Antimicrobial resistance is a major global public health problem, which develops when pathogens acquire antimicrobial resistance genes (ARGs), primarily through genetic recombination between commensal and pathogenic microbes. The resistome is a collection of all ARGs. In microorganisms, the primary method of ARG acquisition is horizontal gene transfer (HGT). Thus, understanding and identifying HGTs, can provide insight into the mechanisms of antimicrobial resistance transmission and dissemination. The use of high-throughput sequencing technologies has made the analysis of ARG sequences feasible and accessible. In particular, the metagenomic approach has facilitated the identification of community-based antimicrobial resistance. This approach is useful, as it allows access to the genomic data in an environmental sample without the need to isolate and culture microorganisms prior to analysis. Here, we aimed to reflect on the challenges of analyzing metagenomic data in the three main approaches for studying antimicrobial resistance: (i) analysis of microbial diversity, (ii) functional gene analysis, and (iii) searching the most complete and pertinent resistome databases. Bacterial resistance, which is closely associated with the use of antimicrobial agents, is considered one of the most persistent global public health problems . HoweverAntimicrobial resistance  developsAlthough numerous recent and ongoing research efforts have addressed bacterial virulence and multi-resistance mechanisms, the processes governing bacterial fitness, competition, dissemination, and adaptability remain poorly understood. Little is known about the diversity, distribution, and origin of resistance genes, especially those of most environmental bacteria that cannot be cultured under laboratory conditions . The devin vitro. The definition of community structures allows a deeper understanding of the relationships between individual components of a community and their dynamics in response to the selective pressure of a space-time parameter  enzHowever, an increasing number of resistance studies have provided new insight into microbial pathogenicity by analyzing the ARGs of both pathogenic and non-pathogenic bacteria . This woThe most comprehensive approach for metagenome sequencing is complete genome sequencing; this approach allows the study of the structural and functional diversities of a microbial community by identifying genes and metabolic pathways and reconstructing almost complete bacterial genomes . The maiComplete metagenomic sequencing, since it was implemented, has had a tremendous impact on the study of structural and functional microbial diversities in environmental and clinical samples and has been an alternative to rRNA sequencing . AlternaHowever, some challenges affect the quality of metagenomic analysis, with the first being low sensitivity in detecting minority populations that harbor resistance genes, which has proved to be an obstacle at the time of analysis . The secHorizontal gene transfer is a common method of genetic transfer between species of the same genus or with similar characteristics . Thus, sTaxonomic classification without the assembly of contigs is a faster approach, with a lower computational cost and no assembly problems . HoweverContrarily, the length of contigs is an advantage for taxonomic classification using contig assembly. Thus, this approach predominantly makes use of databases . MoreoveIn ARG analyses, genome assembly can help differentiate between bacteria in terms of conserved regions like ribosomes, possible HGT regions, and several classes of transposable elements. This is because the reduced size of gene sequences directly impacts gene annotation transfer and studies of biological mechanisms associated with resistance. Thus, taxonomic assignment by contig assembly tends to better facilitate the identification and understanding of resistance mechanisms, such as the understanding of microbiota structural relationship roles in resistome studies. However, it is important to emphasize that researchers must be aware of the type of sample being worked with, if the sample is too heterogeneous and if there is sufficient computational power to analyze the amount of data collected. Even for good-quality, long sequences, taxonomic classification without assembly could be a more appropriate approach from a computational point of view, depending on the dataset and the computational power available .Notably, studying the taxonomic assignments of resistome elements using high-throughput sequencing goes beyond identifying ARGs in host-pathogen relations and can be used to study resistomes in environmental samples, such as those from water reservoirs , hospitaStudying taxonomic signatures enables a better understanding of the relationships between the members of a microbial community. Alternatively, functional metagenomic approach aims to identify functions within the community via the discovery of new enzymes, groups of biosynthetic genes, and ARGs. The functional annotation of a metagenome is similar to its genomic annotation, such that predicted gene sequences are compared to existing sequences in annotated databases . Thus, tThere is a wide range of databases and tools to classify the taxonomic profile of a community and performing functional analyses; thus, the choice of reference database can have important implications for the quality of information obtained. There are three important points regarding sequence- and function-based analyses. First, functional analysis provides an opportunity to perform various sub-analyses, depending on the sequencing depth, including functional category, protein family, gene ontology, protein–protein interaction, pathway, and subsystem analysis. Second, for both types of analysis methods, researchers can work with assembled or non-assembled data. Finally, there are tools, usually open source tools, such as QIIME , Mothur Genomic annotation employs sequence comparison with similarity-based search tools, such as BLAST+, which was developed by the National Center for Biotechnology Information (NCBI) . DIAMONDAlthough there are good database options and tools for comprehensive metagenomic analyses, continuous improvement for the detection and characterization of genetic elements is necessary, as it is important for understanding resistance acquisition over time and evolutionary dynamics. Thus, resistome databases must be constantly updated to include newly identified variant sequences, inserts, and deletions to improve our understanding of these variations in context of resistance . Moreove1 database and ARDB (both now defunct). ResFinder also sources information from published literature, including reviews . Its first version integrated ARGs from ARDB and CARD, and redundant sequences were removed. When it was updated in 2018 , proteinResfams is organized by ontology with a curated database of protein families and associated profile hidden Markov models (HMMs) and protein sequences from the CARD database, the Lactamase Engineering Database, and Jacoby and Bush’s collection of curated beta-lactamase proteins. It was designed to quantitatively understand the relationship between human and environmental resistomes, with an analysis of over 6000 microbial genomes. It was last updated in 2018 .Although the databases fully complement one another and are often redundant, they continue to be cited as having individual specificities for particular datasets, which hinders recommendations. Given the importance of studies on microbial resistance and the quality of data obtained, it is essential that a platform-independent dataset be available for the antibiotic resistance research community. In one sequence database (DNA/Protein/raw data sequences), INSDC , initiatives for the unification and integration have already been implemented. INSDC is a standardization and unification initiative among the main sequence databases , making the data of these databases effectively interchangeable . This tyMetagenomics is a promising tool for identifying and understanding antibiotic resistance mechanisms, using sequence- and function-based approaches. Notably, however, various analyses of antimicrobial resistance are strongly related to other aspects of the research being carried out, such as mutations, pathogens, metabolic pathways, and gene expression. Reviews analyzing antimicrobial resistance addressing these aspects are strongly recommended.in silico predictions based on machine learning are thus becoming more common and have the potential to predict resistance outside databases. This will allow for the development of high-throughput data analysis approaches and the answering more complex questions regarding antimicrobial resistance.The most important considerations in a metagenomic resistome study are understanding the nature of the dataset being analyzed and the support that is available for its analysis. If one takes into account the large quantity of data and the complexity of the biological mechanisms involved in antibiotic resistance, it may be preferable to adopt reductionist approaches to decrease bias and increase the objectivity of analyses. It is important to emphasize that the costs of algorithms, computers, and analytical tools are decreasing; SA and VA wrote the manuscript, as well as guided and reviewed the work. JP revised the writing and formulated the tables. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The present review article provides an overview of the properties of various natural and synthetic fibers for the fabrication of pure natural composites and the combination of both natural/synthetic fibers-based hybrid composites, bio-based resins, various fabrication techniques, chemical and mechanical properties of fibers, the effect of chemical treatment and the influence of nanoparticles on the composite materials. Natural fibers are becoming more popular and attractive to researchers, with satisfactory results, due to their availability, ease of fabrication, cost-effectiveness, biodegradable nature and being environmentally friendly. Hybrid composites made up of two different natural fibers under the same matrix material are more popular than a combination of natural and synthetic fibers. Recent studies relevant to natural fiber hybrid composites have stated that, due to their biodegradability and the strength of individual fibers causing an impact on mechanical properties, flame retardancy and moisture absorption, natural fibers need an additional treatment like chemical treatment for the fibers to overcome those drawbacks and to enhance their better properties. The result of chemical treatment on composite material properties such as thermal, mechanical and moisture properties was studied. Researchers found that the positive influence on overall strength by placing the filler materials (nanoparticles) in the composite materials. Hybrid composites are one of the fields in polymer science that are attracting consideration for various lightweight applications in a wide range of industries such as automobile, construction, shipping, aviation, sports equipment, electronics, hardware and biomedical sectors. In recent years, many researchers have been showing an interest in the utilization of natural fibers for the preparation of hybrid composites because of its abundance, low density, recyclability and great strength ,2, NaturOne of the primary drawbacks of using natural fibers as reinforcement in composites is the hydrophilic in nature, which makes them inconsistent with hydrophobic matrices. For refining the inconsistency, the surface treatment of natural fiber is required to advance the global properties of the composite ,8. ApartOver the previous years, there has been an ever-expanding enthusiasm to fuse at least two fillers into a typical matrix. There has been a consistent increment in the quantity of distributed works that are identified with hybrid composites from the past ten years. in view of hybrid composites (between 2010 to 2020) found in the Web of Science and Scopus via looking for the words ‘hybrid composites’ with 26,450 research yields. The development came about because of one goal, to progress the properties of the subsequent composite material to accomplish the wanted properties and improved execution of such composites.Hybrid Composites are the materials that are made up of twofold or more constituent materials, namely matrix and reinforcement ,15. A maIf the compound material is metal fiber then it is called a metal matrix composite, if it is a polymer matrix then it is called a polymer matrix material ,18. The Natural hybrid composite materials contained fibers of great quality and a modulus introduced in a matrix material. Along these lines, every one of the individual materials (fiber and matrix) holds its chemical and physical properties and they give a combination of properties which would not be conceivable if they were utilized alone. Here, the fibers act as the central load-carrying agents and the matrix material encompasses them in position alongside, acting as a load carrying part between them, protecting the fibers from the natural harms of raised temperature and humidity. Accordingly, it could be properly said that the fiber gives reinforcements to the matrix; thus, the name Fiber Reinforced Composite Materials (FRCM).Reinforced hybrid materials are made by joining at least two distinct varieties of fibers in a distinctive matrix material. Hybridization of two sorts of filaments with particular lengths and widths offers a couple of central focuses over the use of both of the strands alone in a lone polymer lattice. Most studies are on the hybridization of regular filaments with glass strands to upgrade the properties. They have average calorific regard and cause little stress, similar to prosperity, wellbeing and protecting Also, they show amazing mechanical properties, have a low thickness and are modest ,19,20,21Composite materials classified on the basis of a matrix serve as a binder and a reinforcement, which acts as a filler material. Metal matrix composites (MMCs) have numerous advantages over solid metals such as great strength, modulus and better-quality properties at raised temperatures. As a result of these qualities, metal matrix composites are getting looked at for a wide scope of applications. On account of their high thickness, they are not greatly requested. The most commonly used metals in the MMCs are steel, tungsten, boric and, molybdenum ,23.Ceramic matrix composites (CMCs) and carbon-based composites are examples of inorganic  composite materials. The main aim of CMCs is to improve the toughness of the composite materials  and theyThe organic matrix composites (OMCs) are broadly classified into polymer matrix composites and carbon-carbon matrix composites. Polymer composites are the most popular and commonly used matrix materials. The mechanical properties of polymeric composites are easily applicable to a wide range of structures because of their desirable mechanical properties, such as low mass, high stiffness and high-temperature resistance. When compared to the metal and ceramic composites, polymer composites have less strength and stiffness; to overcome this problem, composites are reinforced with other materials. The handling of polymer composites need not include high temperature and pressure. Likewise, the equipment required for the fabrication of composites is more straightforward. Therefore, polymer matrix composites quickly became famous and of interest for many researchers in terms of basic applications. Composites are utilized in light of the fact that the general properties of the composites are better than those of the specific segments.Polymer composites are further classified as thermosets and thermoplastic composites. Thermoplastic materials are solids at room temperature; heating is required to soften or melt the material to place it into the mold and then it is cured to get the desired shape. These are recyclable. Thermosetting polymers are in both liquid and solid form and these are not recyclable. In thermoplastics, the atoms are bonded by covalent bonds whereas thermosetting polymers have cross-linked bonds, because these thermosetting materials are stronger and stiffer than thermoplastics. Thermoplastic materials include polyamides, polyoxymethylene (POM), polycarbonates (PC) and acrylics. Thermo setting materials include epoxies (EP), thermoset polyamides, amino plastics and polyester thermosets (TS) .Fiber Reinforced Polymer Composites (FRCs) are the most widely used composites and are composed of fiber and matrix. Fiber serves as a reinforcement and acts as a stiffness agent. The matrix material glues all fibers together and acts as a stress distributor among the fibers. Sometimes, the filler material is added to smooth the fabrication process. Depending upon the availability, reinforcements are classified into natural and synthetic fibers. Though there are many advantages to synthetic composites, there are some disadvantages. Synthetic fibers burn more quickly than natural fibers. Extra electrostatic charge is produced by rubbing them with natural fibers ,25.Natural fibers are produced from animal (protein is the main component), plant (cellulose is the main component) and mineral based resources. Natural fibers have advanced physical and mechanical characteristics when compared to the other fibers. They are readily available in nature and also biodegradable ,27. BecaThe chemical composition plays a significant role in fiber materials and it depends on the fiber source. It varies from fiber to fiber and also within the family as shown in There are various man-made or synthetic fibers that have been brought into recent research networks with respect to their remarkable properties. The mechanical properties of synthetic fibers are shown in Natural fibers are not defect-free materials even though they have great qualities when compared to the other advanced fibers. They have strong polar bonds, which may affect the bonding capability in the polymer matrix . To avoiA matrix material is one which plays an adverse role in the composite material. The shape, durability and surface properties depend on matrix (resin) material. Based on processing techniques, resin materials are classified into two types, such as thermosets and thermoplastics . A matriResearchers are showing interest in using thermoplastics as matrix materials because of their integral properties, such as low cost, moldability, less weight and recyclability. The main advantages and disadvantages of these thermoplastic polymer materials are discussed below in Kasama et al. investigated the mechanical and thermal properties of sisal and glass fibers as reinforcement and polypropylene as a matrix material , the autHaneefa et al. worked on the tensile and flexural properties of banana and glass fiber reinforced PS composites . It was Thermosets are well known for their exclusive uniqueness of making 3-dimensional bonds after curing. Thermoset resin far differs from thermoplastics and these have improved mechanical properties, thermal stability, resistance to the creep and biodegradability . The merYorseng et al. developed the bio-based natural fibers hybrid bio epoxy composites for the application of semi-structured components and their mechanical behavior under various circumstances was observed . SurfaceSingha et al. worked on the synthesis and characterization of pine needles reinforced resorcinol-formaldehyde (RF) biocomposites . ComposiBio-based polymeric resins are produced from renewable sources. These are classified into three types based on their physical properties. The first one is fully bio-based and biodegradable resins those are polyhydroxyalkanoates (PHA) and starch, the second one is partial bio-based resins those are polylactic acid (PLA) and cellulose and the last one is partial non-biodegradable resins those are polyethylene terephthalate (PET) and polyethylene. Most of these bio-based resins are originated from plants and plants-based sugars. The merits and demerits of bio-based resins are discussed in Hybrid composites are not defected free materials because of the fabrication errors, voids in the composite, weak bonding between matrix and reinforcement, environmental conditions, errors during the development and curing period, scratches on the fiber materials, impurities, unbalanced proportion of matrix and reinforcement affect the total performance of the composite materials . LimitinNowadays researchers are using three types of nanofillers to improve the performance of the composite material. They are classified into three main groups such as nanotubes, nanoparticles and nanolayers. Nanofillers are used based on the particle sizes—one dimensional, two dimensional and three dimensional. Nanomaterials are larger than macro-level particles, individual atoms and also have a huge surface area per unit volume. Most of them are produced from metals, carbon, polymers and metal oxides. Nano clay, carbon nanotubes, carbon black and graphene are the best example of metal-based nanofillers and also widely used nanomaterials.Pappu et al. worked on unused materials, like fly ash and sisal fibers, to prepare the micro and nanocomposites for multifunctional applications . The hanNanoclay particles are one of the most commonly used filler materials due to its availability and inexpensiveness. It comes under the silicate group nanomaterials. Nanoclay particles in the composite material can increase the mechanical, physical and chemical properties. The size and shape of the particles also plays an important role in the composite material for the strength and bonding between reinforcement and matrix material. Toyota automobile industries first started using the nanoclay particles in the polymer composite fabrication ; in thisGenerally, nanoclays are available in several forms such as nanoclay platelets, calcined nanoclay and natural montmorillonite (CB). Assaedi et al. investigated the effect of nanoclay platelets  on the thermal and mechanical properties of fly ash geopolymer . In thisHakamy et al. studied the effect of calcined nanoclay (CNC) on mechanical and microstructural properties of hemp fiber reinforced Portland cement nanocomposites . CalcineEesaee et al. worked on the effect of nanoclay particles in the reinforced glass/woven fiber composites with phenolic resins  and mainAvil et al. observed the effect of porosity and failure strength in the presence of nanoclay in glass fiber reinforced epoxy composites . The resMaharsia et al.  studied Fiber-reinforced composites are better than pure polymer composites. There should be an occurrence of auxiliary applications on account of its high mechanical properties and lower expense. Due to an account of advanced properties, hybrid composites are a replacement for synthetic composites, particularly when it comes to the load-bearing and construction applications . A recenA recent survey stated that the fabrication of fiber-reinforced polymer composites has become more popular in commercial applications, especially in the aerospace industry. The utilization of fiber-based composite caused a reduction in overall weight by 35% of the aircraft, and shows a positive effect on fuel consumption and efficiency of the overall performance. Due to these properties, aircraft industries such as Boeing, Dreamliner and Airbus companies have started using the composites in the majority of their components . The maiSantos da luz et al. worked on natural fiber composites in the replacement of synthetic fiber composites for military applications . They coFilter media: Liquid, gas and molecule filtration.Nano-sensors: Biochemical, thermal and piezoelectric sensor.Cosmetics: Skin cleaning and healing.Life science: Drug delivery carrier and wound dressing.Tissue engineering scaffolding: Porous membrane for skin, 3D scaffolds for bone and cartilage regeneration.Industrial applications: Micro/nano electronic devices, electrostatic dissipation, LCD devices, lightweight space craft materials.In this review paper, fiber-based hybrid composites have been evaluated, specifically on account of their properties such as surface morphology, thermal stability, dynamic mechanical, mechanical, moisture absorption, fire retardance and applications. Hybridization became famous, not just because of the improved presentation of the subsequent items, but also due to the possibility of conquering the confinements that hamper the relevance of common filaments in specialized structures. There is an immense chance that a huge level of natural fibers can be consolidated in ordinary engineered fortified composites items, which is a major advance from biological and affordable perspectives. The quality natural fibers rely on the development conditions and development time affects the performance of the composite. Although there are so many advantages to using natural fibers in commercial applications, it is bounded to some of the applications because of its biodegradability and flammable properties compared to synthetic fiber composites. To overcome this problem, the researchers started to work on chemical treatment of natural fibers under various conditions. These modifications improved the fiber strength and also bonding capacity between matrix and reinforcement. On the other hand, the researchers found an interest in the integration of nanofillers into composite materials. The addition of nanoparticles to the hybrid composites played a crucial role in advancing their properties. The surface properties, fracture toughness, void elimination, amount of water absorbed is decreased and the dynamic mechanical properties are increased because of these nanofiller materials in the hybrid composite. It is worth saying that hybrid composite materials bring a revolution in the real-life commercial applications such as biomedical, aerospace, shipping industry, automobile, biomedical, construction, drug delivery, wound dressing and gas filtration applications. In the future, the alterations in fabrication techniques and the addition of nanofillers may lead to improvement as well as prediction of the results is possible, which attracts researchers to use it in multiple applications.


Over the past few years, an intense discussion about the reproducibility of scientific findings in various life science disciplines arose  briefly discussing the role of the experimenter in animal studies, (2) investigating the advantages and disadvantages of automated test systems, (3) exploring the potential of automation for improving reproducibility, and (4) proposing an alternative strategy for systematically integrating the experimenter as a controlled variable in the experimental design. In particular, I will argue that systematic variation of personnel rather than rigorous homogenization of experimental conditions might benefit the external validity, and hence the reproducibility of behavioral data.As impressively illustrated by the above-mentioned multi-laboratory study, environmental conditions can exert a huge impact on behavioral traits. This has been particularly highlighted in the context of behavioral genetics, where experimental factors have been observed to interact greatly with trait-relevant genes. In order to identify and rank potential sources of such variability, Chesler et al. initially applied a computational approach to a huge archival data set on baseline thermal nociceptive sensitivity in mice , it cannot be ruled out that the human observer may evaluate observations inconsequently and that definitions of behavior in, for example, ethograms are interpreted in various ways. Training deficits as well as a lack of inter-observer reliability can thus be regarded as additional sources of the experimenter-induced variation  Automation of recording and test approaches, and (2) development of automated home cage phenotyping, or alternatively, test systems that are attached to home cages and can be entered on a voluntary basis. Whereas, the former involves testing the animal outside of the home cage and thus still requires handling by an experimenter  known to induce or explain a lot of variation in behavioral studies. This way, conditions within experiments are more stringently homogenized, increasing the risk for obtaining spurious findings. Instead of trying to eliminate this variation, one may therefore think about systematically including it to improve the overall robustness of the data. Building on previous heterogenization studies (e.g., Richter et al., From a practical perspective, such an approach may be associated with certain challenges, especially for small research groups with limited resources. For bigger research organizations or large-scale testing units, however, the organizational efforts might increase only marginally. Balancing overall costs and benefits, such an experimenter-heterogenization may still represent an effective and easy-to-handle way to maximize the informative value of each single experiment (see Richter, The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with the author SR.


The increasing availability and complexity of next-generation sequencing (NGS) data sets make ongoing training an essential component of conservation and population genetics research. A workshop entitled “ConGen 2018” was recently held to train researchers in conceptual and practical aspects of NGS data production and analysis for conservation and ecological applications. Sixteen instructors provided helpful lectures, discussions, and hands-on exercises regarding how to plan, produce, and analyze data for many important research questions. Lecture topics ranged from understanding probabilistic  genotype calling to the detection of local adaptation signatures from genomic, transcriptomic, and epigenomic data. We report on progress in addressing central questions of conservation genomics, advances in NGS data analysis, the potential for genomic tools to assess adaptive capacity, and strategies for training the next generation of conservation genomicists. Informing conservation efforts is one of the most important and challenging needs of the genomic era (https://cibio.up.pt/congen/index.html), the molecular and computational tools accessible to conservation have grown in number and matured  such as hybridization, inbreeding, population structure, and loss of genetic diversity . Today, Throughout this genetics-to-genomics transition, many authors, including those of previous ConGen workshop reviews, have reflected on this paradigm shift. They have noted the best practices for data production and quality control (filtering), experimental design, computational approaches, career guidance, and the increasing roles of women , and proDefining biologically meaningful management units within species is challenging . For conWith genomic data, we can now identify loci, alleles, and surrounding chromosomal regions associated with adaptive differentiation, which improves our capacity to define ESUs while taking into account both demographic and selective processes . IncorpoBox 1.Oncorhynchus tshawytscha) and steelhead (O. mykiss) have distinct spring (premature) and fall  migratory phenotypes  in several river basins across western United States. The spring-run phenotype differs substantially in behavior and physiology but has declined in abundance throughout the ranges of both species. Spring-run phenotypes have ecological, economic, and cultural importance, and are valuable to commerce and ecosystems for their greater fat content  of the United States? Chinook salmon  between premature and mature migrants within local rivers was found by multiple studies  is vulnerable to loss and unlikely to reappear for a long time if lost from a population. Populations where  the ESA . In Febr the ESA .These studies and the resultant legal action have recharged debate over whether, when, and how species should be managed for single genes . A conceNe) is one of the most important concepts and parameters in conservation and evolutionary genetics because it influences the rate of loss of genetic variation, the levels of individual inbreeding, and the effectiveness of natural selection and gene flow  is taken into account  improves reliability of confidence intervals and reduces bias in estimating omosomes . TogetheNb, or the number of effective breeders in a cohort, as a promising parameter for genetic and population management because of its intrinsic relationship to Ne and potential relationship with population abundance or environmental conditions  information on population status, rather than having to wait to sample between generations which is often required by temporal estimations of Ne  highlighted Nb through recent studies of brook trout . He cautioned that while estimates of Nb can track abundance in some species , requiring only a single sample per generation  have increasingly been the main focus . Of 33 pAt ConGen 2018, methods both currently applied widely and those only recently employed in conservation genomics were discussed. Paul Hohenlohe (University of Idaho) reviewed the many variations and utility of RADseq . The major improvements prescribed by the bestRAD protocol are the ability to reduce the proportion of PCR duplicates, efficiency in using smaller starting quantities of DNA, and efficiency in scaling from hundreds to thousands of samples (Lectures by Hohenlohe and Seth Smith (University of Montana) demonstrated the utility of Rapture  and does not include labor for the data production, which is often the majority of the cost. The cost of sequencing depends on the desired coverage. The number of samples that can be multiplexed per sequencing lane is a function of the number of targeted loci, the PCR duplication rate, and the proportion of reads that do not that align to targeted loci. He cautioned that the PCR duplication rate and proportion of off-target reads are expected to vary depending on the proportion of RAD loci targeted for capture and the total number of loci in the original RAD library which can be influenced by sample quality and PCR duplicate rates, and are typically 20–30% but can be >80%  samples are pooled early in the bestRAD protocol, the cost of the library preparation kit and capture reaction scales well for large sample sizes. For instance, up to 96 uniquely indexed individual samples are pooled prior to adding sequencing adapters and amplifying the library using a commercially available kit. Seth Smith estimated that bestRAD libraries can be generated for F-statistics of removing PCR duplicates and aligning to a reference or not. These choices depend on genetic and financial resources available, local laboratory expertise, and the study question. Useful sensitivity frameworks for assessing RAD locus assembly, the benefits of a reference genome, and the effects of PCR duplication have been described elsewhere . These advances in Stacks hold promise to advance RADseq analysis in conservation genomics by yielding more accurate genotypes and longer haplotypes  across biological and temporal scales , though Still, there are surprisingly few studies that employ these techniques to inform conservation. Perhaps this is due to fewer labs having the capacity to produce and analyze these potentially tissue- and time-specific data, the actual and perceived conflicts in evolutionary paradigms, or the ongoing discussion regarding the role of plasticity in long-term population persistence . RegardlAt ConGen 2018, participants gained exposure and experience to transcriptomics through an interactive lecture on data production and hands-on analysis of differential gene expression led by Joanna Kelley (Washington State University). Participants learned how to functionally annotate variants of interest and perform enrichment analysis with instructor Mackenzie Gavery (University of Washington) and an epigenomic data set. Here we highlight Gavery’s lecture demonstrating the potential utility of epigenomics in conservation with a recent study of DNA methylation of cytosine residues at CpG sites induced by hatchery conditions ; Box 2.Box 2.How will changes in DNA methylation influence adaptation to artificial environments in hatchery fish?Oncorhynchus mykiss), A common goal of captive breeding programs is to support declining wild populations ; however, there is concern that rearing in artificial conditions may inadvertently reduce fitness. In conservation salmonid hatcheries, there is mounting evidence that tank-rearing conditions can induce developmental plasticity and impact life-history traits. To examine the role of epigenetic changes in hatchery-reared steelhead trout . Also of discussion was the increasing availability of R packages to efficiently analyze and visualize NGS data sets and results and the importance this has in increasing reproducibility and reliability, and lowering the barrier on bioinformatics and data analysis in general , Joanna Kelley, and Brenna Forester (Colorado State University). Kelley, for example, provided instruction and materials for transcriptome assembly and quantifying differential gene expression , assessing population genomic vulnerability, and using adaptive genetic information to identify conservation units. New approaches have emerged for cheaper genome-wide data production  and data analysis . Emphasis in recent years at ConGen including the use of tools becoming more cost-effective and available to conservation genomics including DNA capture, transcriptomics, epigenomics, genome-wide, and reference-genome-based work. The purpose of ConGen remains to introduce recent novel techniques and approaches to a wide range of participants from different career paths, institutes, and countries. Recent work by ConGen workshop instructors and other researchers has expanded the types of data used in conservation genomics at large (e.g., see transcriptomics and epigenomics and de novo genome assemblies to RADseq to differential gene expression among populations and more. Although the amount of genomic data production grows exponentially, the continuing challenge for genomicists remains in obtaining a solid foundation in population genetics theory, data filtering, and computational analysis. Through training and experiences such as those available at workshops like ConGen 2018, the modern conservation and population genomicist will be able to examine a wide range of central questions, evaluate the appropriate tools for data production and analysis, and integrate across different data types from RADseq to whole-genome resequencing, RNAseq, and more. As population genomics continues to evolve, we hope this review of ConGen 2018 will help serve as a benchmark, motivation, and starting point for information and references for readers from world-wide to advance multiple disciplines including conservation, ecology, and evolutionary genomics.In conclusion, major conceptual advances discussed at ConGen 2018 include estimating the effective population size per cohort or generation (e.g.,


As organisms whose life-cycles are intrinsically antimicrobial, prokaryotic predators can profoundly affect the composition of microbiomes, including those underpinning human health, disease, agriculture, environmental, and industrial processes. Our understanding of prokaryotic predators has become increasingly mechanistic as technical advances have allowed us to probe whole cells, populations and ecosystems, identifying the genes and gene products responsible for predatory activity.However, there is still much to learn about the molecular mechanisms of predation, the relevance of those mechanisms to predator biology/ecology and the potential for their exploitation to benefit humanity. The purpose of this Research Topic was therefore to gather together research and theories investigating the mechanisms of predation by prokaryotes.Bdellovibrio and like organisms).The Research Topic has drawn together eight submissions, which together focus on the two best-studied prokaryotic predators, myxobacteria and BALOs , which detoxifies the antimicrobial compound formaldehyde. Addition of Fdm increased the predatory activity of myxobacterial strains against formaldehyde-secreting Pseudomonas aeruginosa, suggesting that formaldehyde secretion is a predation-resistance trait of some prey organisms. The Original Research by Contreras-Moreno et al. shows that copper accumulates in the extracellular space between predatory Myxococcus xanthus and prey Sinorhizobium meliloti cells. The predator expresses copper-resistance genes, while the prey cells produce melanin, which can protect against oxidative stress. By disrupting genes required for copper-induced melanin production, it was shown that if S. meliloti is unable to produce melanin, it becomes more susceptible to predation by M. xanthus, suggesting melanin is another mediator of prey cell predation-resistance.Unlike BALOs, myxobacteria are epibiotic predators, secreting antimicrobial metabolites and proteins into the extracellular environment where they kill and digest prey cells from outside. Three pieces of Original Research in the Research Topic investigate molecular mediators of predatory activity in myxobacteria. S. meliloti forms symbioses with legumes, promoting plant growth, myxobacteria are also generally considered to be plant growth promoting, by preying upon plant pathogens. Adaikpoh et al. investigated the response of myxobacterial predators to the plant phytohormone methyljasmonate. In their Original Research article, they showed that Archangium sp. strain Cb G35 responds systemically to methyljasmonate exposure with pervasive changes throughout its transcriptome and metabolome. The phytohormone caused an increase in swarm expansion and lytic enzyme production, which suggest that the plant uses methyljasmonate to recruit a subset of predatory myxobacteria to the plant.While nitrogen-fixing Bratanis et al. who highlight a variety of ways in which BALO biology and gene products could be used in diverse industrial and medical arenas. Given particular attention are the topics of secreted enzymes , biological control, biofilm formation/degradation and bioplastic production. The authors also discuss the potential for genetic engineering of predatory strains and the potential limitations of BALO applications. Potential future applications are also highlighted in the Mini-Review of myxobacterial predation by Thiery and Kaimer. Important aspects of myxobacterial predation considered by the authors include the mechanisms of motility, how prey cells are lysed, and the delivery of predation factors to prey cells. Myxobacteria are well-known for their population-wide multicellular behaviors, particularly fruiting body formation in response to starvation. Predation by myxobacteria can also be considered as a multicellular behavior, and the relationships between predation and fruiting body formation are discussed in the Mini-Review.It is clear from the Original Research articles described above that prokaryotic predator-prey interactions have the innate potential to impact substantially on plant growth. Understanding the mechanisms at play will allow us to rationally exploit prokaryotic predators as biological control agents, and in other applications. Such potential applications are the focus of the Review article by Ezzedine et al. who investigated the distribution of BALOs in Lake Geneva. Using a metagenomic approach to assess microbial diversity, a seasonal and vertical distribution of BALOs was observed, with different taxa dominating at different depths and at different seasons. The abundance of BALO taxa was found to correlate positively with a number of non-BALO taxa including myxobacteria—potentially reflecting their taxonomic closeness, and/or their shared predatory lifestyle.The ecological importance of prokaryotic predators is the topic tackled in the Original Research by In conclusion, new insights gained by studies such as those included in this Research Topic on Mechanisms of Prokaryotic Predation are likely to be crucial in allowing us to rationally perturb microbial community composition, and deliver predation-inspired improvements in health, food security, industry, and the environment.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Most articles implemented activities that were aligned with community capacity dimensions of citizen participation , community power , leadership , and networks ; few articles identified a direct policy change , and many articles discussed the policy implications of findings for future work . This review synthesizes three decades of efforts to reduce environmental inequities and identifies strategic approaches used for strengthening community capacity.Environmental justice (EJ) efforts aimed at capacity building are essential to addressing environmental health disparities; however, limited attention has been given to describing these efforts. This study reports findings from a scoping review of community–academic partnerships and community-led efforts to address environmental inequities related to air, water, and land pollution in the United States. Literature published in peer-reviewed journals from January 1986 through March 2018 were included, and community capacity theory was applied as a framework for understanding the scope of capacity-building and community change strategies to address EJ concerns. Paired teams of independent analysts conducted a search for relevant articles ( As articulated by Dr. Robert Bullard and other prominent scholars and leaders in the environmental justice (EJ) movement, “everyone is entitled to equal protection and equal enforcement of our environmental health, housing, land use, transportation, energy and civil rights laws and regulations” , in all The patterning of environmental inequity has received great attention and many studies have highlighted the pervasive nature of race as one of the most critically important predictors of exposure to environmental hazards ,14,15. NThe Principles of Environmental Justice, developed in 1991 by delegates of the First National People of Color Environmental Leadership Summit , stress The practice of building capacity focuses on strengthening the characteristics that enable a community to identify, mobilize, and address social and public health problems . Howevercommunity capacity theory as an organizing framework to better understand the strategies used to mobilize communities and address environmental problems ; or an unspecified source of funding.The ‘community demographics’ variable classified studies by the reported race/ethnicity of the community , as well as whether the community was described as low income, impoverished, or underserved.Identified pollution concerns were categorized as: air pollution/air quality concerns; illegal dumping; hazardous waste inclusive of brownfields, Superfund, chemical contaminants, soil contaminants, fish contaminants; and/or water quality concerns related to drinking water or groundwater.PSE outcomes included: reduction/clean-up/remediation; mitigation of pollution; enforcement of laws or review of permits or increased compliance; prevention of industrial development; and/or legislation to address pollution. Failed policy outcomes were coded separately as failures.Studies were categorized as using theory if they mentioned, identified, or used any reference to a social science theory, model or framework. If a theory was used it was identified and its study application was categorized as one of the following: (1) informed data collection instrument; (2) informed sampling methods; (3) identified constructs as a guiding framework for analysis; (4) developed as a result of analysis ; (5) mentioned in the introduction/discussion but not operationalized or measured; or (6) there was no mention of a guiding theory.Our classification of strategies for organizing around environmental pollution concerns were informed by Freudenberg’s intervention strategies to increase community capacity to protect against environmental stressors . In thisIn addition to these capacity-building strategies, the following strategies were author identified through an iterative process of reviewing EJ literature: civil disobedience, letter writing, litigation, media advocacy, partnership, coalition building, and policy advocacy  were that the article was a survey assessing the environmental concern without translation of findings to the target community; or the article did not describe how the study findings were used to assist community in making environmental change.A total of 8452 unique articles were identified by our search , of whicn = 49) followed by a small percentage comprised of community-based entities and foundations  and others . Many authors also described the communities in which their studies were conducted as being predominantly African American , Latinx , or did not describe a specific target community’s race or ethnicity .As shown in n = 41), followed by evaluation studies  and mixed methods research ; with only a few examples of cross-sectional , experimental (1.7% n = 1), or longitudinal  studies.The majority of the articles we identified that satisfied inclusion criteria were case studies . We found fewer studies focused on illegal dumping  or water quality alone . Close to one-third  of the studies focused on multiple pollution issues.The two most common environmental priorities described in the studies were air quality  or a direct policy change . More than one-third of the studies we identified as satisfying inclusion criteria detailed having an environmental impact in some regard , such as the reduction of exposure to an environmental pollutant, the cleanup or remediation of pollution concerns, or another environmental effort . Regarding policy-related outcomes, about one-third of studies  reported mitigating the environmental concern by reducing the risk of the community to the exposure of the environmental pollutant . We identified fewer examples of legislative resolutions to address environmental concerns  or successful prevention of industrial development . A small percentage  reported being able to encourage enforcement of an existing environmental law, regulation, or review of a conditional permit). Fewer studies  discussed other policy-related outcomes such as implementation of new local policies  and several studies discussed failed advocacy efforts in making policy change .Many of the studies we identified did not result in any environmental change . Among these, the most popular mention of theory was related to community capacity  followed by an environmental justice framework . When applied, theory was commonly used in the introduction or discussion as a reference point for framing of the central issue , without being operationalized or measured. Additional application of theory was seen in the development of constructs for analysis , informing data collection measures , or informing sampling methods .More than half of the studies we identified reported using a theory, model, or framework ; the implementation of empowerment approaches ; and community organizing/social action  that encouraged people to advocate for themselves and make demands for increased resources. CBPR was also a common strategy  in which community members participated at varying levels in the selection of issues, study design, interpretation of findings, and dissemination , litigation , and policy advocacy  with less frequent mentions of citizen science activities , civil disobedience , photovoice , and letter writing .Other community change strategies described for enhancing capacity to address pollution concerns see  includedn = 22), displays of critical reflection , identification of community values , and implementation of skills development . About two-thirds of included articles discussed activities related to establishing a sense of community  and the identification of resources . The most discussed activities in our sample of studies included citizen participation , community power , leadership , and networks . Examples are detailed below that represent these most commonly cited dimensions.While we found the concept of community capacity only explicitly discussed in a few articles ,84,85,86In the context of community capacity theory, citizen participation entails the involvement of a diverse group sharing different interests and perspectives for defining a problem and taking collective action . When thIn the context of community capacity theory, community power represents the ability to create or resist and be influential with respect to changing conditions . When thThe dimension of leadership in community capacity theory represents the ability of a person or group to direct and encourage participation, and the sharing of information and resources among a network of community participants . SeveralThe community capacity theory dimension of social and organizational networks encompasses the supportive interactions between groups of people and organizations, formation of new partnerships, and shared decision making . PartnerThis scoping review of capacity-building efforts to address EJ concerns identified a variety of capacity-building strategies at the community level, including community-engaged partnerships and community-led efforts that have been employed to address pollution-related environmental inequities. We have focused on understanding the presence of capacity dimensions and subsequent efforts used to enhance a community’s capacity, as these are fundamental within the context of EJ advocacy in promoting solidarity and generating power to overcome inequities. The ultimate goal of building capacity and cultivating partnerships is to address problems, which often requires enacting meaningful change at the system, structural, and policy levels. However, these types of change are often shaped by local context and may require more time than the span of any research study. Therefore, we consider a range of strategies discussed across published studies as potentially relevant for EJ progress, whether or not these studies explicitly describe impactful PSE change.There were numerous studies that identified and incorporated some type of social science theoretical model for informing data collection, sampling methods, and/or framing study findings within an EJ context ,121,122.In the application of community capacity theory within the context of EJ advocacy, we used the Freudenberg et al.  expandedIn contrast, a second set of activities less frequently documented in these case studies was explicitly focused on considerations for effecting change. About half of the articles highlighted activities related to social and financial capital (resource development), while even fewer articles highlighted capacity-building strategies involving reflection on past community successes or limitations . Similarly, there was little attention given to activities related to strengthening the understanding of root causes (community history); offering of technical assistance or skills development opportunity (skills development); or alignment of the research with community values .Across these observations it is important to note that all dimensions are viewed as instrumental for building capacity; however, many of the dimensions ascribed to the first set are comprised of activities that are more superficial: for example, engagement was often limited to mere study participation. This sort of limited approach to community participation tends to emphasize academic priorities without emphasizing the practices and activities that are necessary to foster community buy-in, shared understanding, community cohesion, or program sustainability. In contrast, the second set of capacity-building activities were utilized less often yet they may be the most critical for deeper engagement and prioritization of community-driven needs and values. While likely necessary for establishing trusting relationships, understanding context, aligning with community priorities, and supporting community development, this second set of activities also require greater intention and investment.This review highlights some of the breadth of the community capacity-building strategies employed in pollution-related EJ efforts, as documented in peer-reviewed journals, and is aligned with scholarship on the importance of building capacity ,131,132.This review was systematic in identifying peer-academic reviewed literature on community EJ research conducted in the United States, published in English. As such, it paints a clear picture of academic EJ community practice over several decades, but it may not be representative of the large swath of the EJ capacity-building efforts not documented in peer-reviewed academic journals. The academic literature alone is inadequate for fully characterizing which capacity-building strategies are most effective in EJ. The modest reporting of PSE change outcomes within the sample of identified studies unfortunately precludes comparative effectiveness claims about which community capacity-building strategies are more likely to lead to desired PSE change even within the space of academic-community partnerships. Even if ultimate PSE change outcomes were known, it would be challenging to make synthesizing inferences from this literature, as varying methodologies are used across studies, research designs are incomparable, the application of the term capacity and the related strategies are inconsistent across studies, measurement tools varied across studies, and there is great variation in community-specific challenges.This review provides an overview of activities for building capacity and working toward environmental community change; and to our knowledge is the first review of its kind to synthesize a myriad of community-led and community–academic partnership activities in this way. One of the major strengths of this review is the inclusion of multiple databases being reviewed by two independent analysts, and the application of a community capacity theoretical framework. The asset-based model of community capacity that we applied in this review clearly distinguishes 10 dimensions and offers one approach for operationalizing strategies with these dimensions. We have identified several examples of deep community capacity-building strategies that may benefit the EJ research community. Through clear and intentional application of a theoretical framework, we can systematically identify common strategies for building capacity and begin to identify research questions related to how best to strengthen community capacity to address EJ concerns. Accordingly, it is our intention that the findings of this scoping review can aid in improving the practice of community-engaged EJ research and enable future research that gives greater insight on what makes for transformative change.


Such a space, is believed to represent what was once defined as Wirchov-Robin space which is thought to be in anatomical connection with the meningeal lymphatics that ultimately drains the lymph flow outside the brain. This is why the imaging of the glymphatic spaces at the level of the dura mater allows to study the anatomical connection between nervous and immune system. The maturation of this space is described in this Research Topic , and its altered function may play a role in specific developmental disorders such as the posthemorrhagic hydrocephalus of prematurity, where the role of neuroinflammation was emphasized . The relevance of the glymphatic space is demonstrated in multiple sclerosis . Moreover, such an altered cross-talk is thought to play a role also in degenerative disorders, such as Alzheimer's disease (AD), cognitive impairment , showing that T helper 17 (Th17) cells, immune cells which are known to be important in the defense of the organism against extracellular infectious agents, are involved in cognitive impairment, multiple sclerosis, ischemic brain injury, and AD. In keeping with these molecular mechanisms, an article of the Research Topic discusses the mechanisms by which Th17 cells enter the brain and induce brain damage. This evidence emphasizes both direct and indirect mechanisms, including direct effects of IL-17 on brain cells and indirect effects due to disruption of the blood-brain barrier, neurovascular dysfunction and gut-brain axis. In keeping with molecular mechanisms, circulating nucleic acids play a fundamental role as shown here by an article  disclosing how fragments of mitochondrial DNA (mtDNA) are released outside the cell and persist in extracellular fluids as circulating, cell-free, mtDNA (ccf-mtDNA). When compared to nuclear DNA, such a double stranded mtDNA is more resistant to nuclease degradation. The bridging between immunity to neuronal activity was further analyzed at intracellular level  showing how the ubiquitin proteasome may sustain communication between neurons, glia, and brain circulating T-lymphocytes both in baseline and pathological conditions. Upregulation of the immunoproteasome to the detriment of the standard proteasome, is implicated in the inflammation. Dysregulations of the immune-proteasome translate into altered communication between neurons, glia, and immune cells.Innate and adaptive immunity are intensely connected with the central nervous system (CNS) including both spinal cord and the brain. Functional studies shed the basis to define a cross talk between the immune- system and the brain in previous decades. Nowadays a number of research manuscripts indicate a strong interaction between the immune system and neural cells involving both glia and neurons, which is evident also by studying the brain structure. Since most adaptive and innate immune cells reach out the brain through blood and lymphatic vessels, the interconnection recruits along with neurons and glia also the whole brain vessels and their innervation. Thus, the anatomical basis of the cross-talk between the immune system and the brain can be identified in each compartment hosted in the gray and white matter of the CNS. These anatomical connections are analyzed at multiple levels ranging from electron and light microscopy In summary, the Research Topic provided multi-level anatomical evidence concerning a bi-directional communication between nerve- and immune- cells showing that altered communication between the immune and nervous system is a common hallmark in neuro-developmental, neurodegenerative, and neuro-immunological diseases.FF and FO equally contributed to writing and editing the editorial.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term. In recent years, statistical genetics and bioinformatics have made progress in the prediction of risk for different complex disorders, i.e., those diseases characterized by several genetic and environmental influences . In partGenetic susceptibility and environmental exposure alone are not sufficient to explain the pathogenesis of noncommunicable diseases, but should be integrated into a more complex scenario that can manifest pathological phenotypes. Epigenetics is a crucial component of this scenario, as its variations are linked to specific exposures that might be able to highlight the effects of the environment on the genome .Scientific evidence has established that a healthy diet enhances life expectancy and helps prevent diseases. Although in the last few decades there has been huge growth in knowledge of the relationship between dietary components and diseases, the biological mechanisms underlying these effects are not yet well understood . NutritiAnother emerging health determinant is microbiota status. The human microbiota consists of a complex ecosystem of microorganisms that live in the human body. Most of the microbial population is in the gut . The ratThe increasing development of genetic tests has made the evaluation of their risks and benefits crucial to their appropriate translation into clinical practice, especially in the case of the COVID-19 pandemic ,11,12.In this review, an overview of the public health implications is given, focusing on the Italian context. The building of health professionals’ and citizens’ omics sciences literacy is discussed, as well as the different regional departments’ perspectives.In the last few decades, genome-wide association scans (GWAS) have been used to identify the genetic basis of chronic diseases, which revealed the influence of several common genetic variants on their risk. These conditions include but are not limited to cardiovascular disease (CVD) ,14, cancSince these variants usually show a small effect size, they are generally condensed into polygenic scores (PGS), also known as polygenic risk scores, when dealing with diseases . These aAs a consequence, the integrated use of PGS with other risk algorithms using environmental factors has been proposed to predict the risk of chronic conditions in common clinical practice . Among tEpigenetic biomarkers represent a means by which lifestyle and environment can be taken into account in the study of health and disease ,34,35. DThe field of oncology is so far the most developed in terms of epigenetic biomarkers. A recognized signature of most cancer types is genome-wide hypomethylation, a hallmark of genome instability, alongside gene-specific hypermethylation  . The latGNAS [ZBTB12 [BRCA1, and CRISP2 [Epigenetics is known to play a role in both neurodegenerative and neuropsychiatric diseases, as DNA methylation changes have been described in Alzheimer’s disease , ParkinsGNAS ,65,66,67 [ZBTB12 ,69, BRCAd CRISP2 . The disOne important limitation on the use of epigenetic biomarkers in clinical practice is the tissue-specificity of the methylation patterns, so ideally the target tissue of the disease should be used. Despite this limitation, more and more studies are testing circulating blood as surrogate tissue for epigenetic analysis. Blood is a good source of DNA, obtained from noninvasive liquid biopsy, and is already used for epigenetic biomarker design in clinical practice for many human diseases ,71. DNA Very recently, cell-free DNA (cfDNA) epigenetic research has been gaining more attention as a possible means to identify and predict tissue damage or the origin of certain pathological conditions . CancerLDespite their usefulness, the sensitivity and reproducibility of liquid-biopsy-based methods using cfDNA still need to be improved, especially in those applications working with a very low amount of starting sample.Beyond the lack of evidence of clinical utility for these scores, some issues remain in the field, like transethnic applicability  and ethiThere is the need for large prospective population-based studies with a large amount of data collected with standardized methods, along with biological samples collected and stored in a biobank. In Italy, recently, the Moli-sani cohort study  . These epigenetic changes show long-term stability; accordingly, the epigenetic pattern may be considered a record of environmental exposures experienced throughout life . The patterns of miRNA alterations are specifically related to the type of environmental pollution to which the organism has been exposed. In studies where smoking-induced changes were investigated, the general observation was a miRNA downregulation of expression, as initially demonstrated in mouse lungs  and therSecondary prevention may be achieved in lung cancer by identifying high-risk individuals using a predictive epigenetic biomarker, such as miRNAs, as analyzed in body fluids. This personalized approach is referred to as “preventive theranostics” and represents an emerging application of personalized medicine to cancer prevention. Researchers are currently publishing various miRNA signatures that respond to environmental exposure and have shown usefulness as biomarkers. The relative expression of miRNAs can be studied by various techniques, such as microarrays, used as an initial approach to finding the potential candidate miRNAs, or quantitative real-time PCR (qPCR), used to validate highly dysregulated miRNAs. Moreover, miRNAs can be sequenced and quantified using next-generation sequencing (NGS) platforms . Due to Future research should focus on (a) identifying the molecular mechanism underlying miRNA expression changes in response to environmental exposures; (b) to determine whether the changes in miRNA expression are an early signal of the pathogenic processes developing in the organism; (c) whether or not this miRNA signature may be used for early detection of cancer identifying high-risk subjects (secondary prevention); and (d) whether miRNA alterations are drivers or passengers in the ongoing carcinogenesis process. The use of miRNA containing microvesicles is a hot topic in research on the early diagnosis and prognosis of cancer. Given their stability and abundance in blood serum, miRNAs containing micro-vesicles have been proposed as new diagnostic biomarkers for cancer . ExtraceThe Human Genome Project and the increased use of the omics approach in nutrition science have led researchers to focus on personalized nutrition in order to improve the impact of diet on health status and wellbeing, taking into account individual genetic factors and epigenetic signatures . PrecisiAlthough it is reasonable to expect that, in the future, disease prevention and treatment will be formulated at the individual level according to genomics features, at present, the major challenge for public health genomics is represented by the advance of the scientific evidence necessary to demonstrate if and when the use of genomic information in public health can improve health outcomes in a safe, effective, and cost-effective manner, also taking into account the ethical, legal, and social issues . FurtherHuman‒microbiota co-evolution also follows an intergenerational transmission pattern . The oriFrom such a point of view, the gut microbiota is a selective agent shaping the adaptive evolution of the human diet, phenotypic plasticity, gastrointestinal morphology, and immunity. Therefore, as can be expected, microbiota aberrations (dysbiosis), since childhood, have been associated with a range of communicable ,109,110 The developmental origins of health and disease provide a theory by which to understand the pathogenic pathways that explain early-stage environmental factors such as human gut microbiome modulation . ExposurEnterobacteriaceae and an increase in the Bacteriodaceae. This shift is due to different feeding practices after weaning. The degradation of complex fibers and carbohydrates improves the role of the microbiota in the host metabolism.The intra-individual (α-diversity) and functional complexity increases with age, while the interindividual variations (β-diversity) become less marked. The ratio among the principal observed microorganisms’ families changes with a reduction in the The exposure profiles and the gut microbiota change during such a period may then lead to health and disease predisposition in adulthood and can influence aging. Even if a real interconnection and predictive role of the microbiota modulation is not yet clear for most diseases, the clarification of such processes is the key to achieving health improvement for future generations.From an immunological point of view, various hypothetical models clarify the interconnections of microbiota with the host and the increased prevalence of the disease with an immunological etiology. For example, for type 1 diabetes, five models have been proposed , among wFrom a preventive medicine point of view, knowledge regarding the eubiosis—an equilibrium status that can guarantee the integrity of the gut mucosa—and dysbiosis transitions of the gut microbiota is crucial. The focus could be the identification of validated biomarkers able to describe such a transition. In particular, we need to know about the growth of microorganisms that promote inflammation and the decrease of other groups that can promote host monocytes’ collaboration in human homeostasis. The microbiological methodology seems to privilege a global approach to the complexity of the microbiota, but, on the other hand, a simpler approach based on valid biomarker identification is useful for risk stratification in public health.Bifidobacterium, Akkermansia, and Christensenellaceae.The chronic inflammation described in older people is characterized by a reduction in microorganisms such as A recurrent question for diseases associated with dysbiosis status is whether the dysbiosis is a determinant, a risk factor, or a consequence of the disease. Nowadays, the evidence seems to suggest very early modification of the microbiota in disease, so its preventive role as, at least, an early detection opportunity before clinical onset, is fundamental for better clinical management and prognosis.Dysbiosis not only has an effect on the gut but also on distant organs. Microbial metabolites, such as the induction pathway typical of pathogens and to produce pro-inflammatory cytokines, can reach several organs, also inducing neurodegenerative diseases and cancer. Therefore, even when the identification of the point break between eubiosis and dysbiosis has been identified, how should an intervention proceed? C. difficile infection is fecal microbiota transplantation. However, such therapeutic intervention—validated from an economical point of view for elderly patients—is not yet common in children because it seems to be associated with a high incidence of adverse effects, including severe adverse effects known in adults (>8%) [Different methods have been suggested. The only cost-effective method for the treatment of recurrent vancomycin-resistant ts (>8%) .Another method consists of the development of a target therapy: for example, using selective antibiotics or phages with the purpose of decreasing the bacteria involved in the pathogenic processes. However, such therapies are uncertain both in terms of the unclear definition of the microbial target and the possible adverse effects .Lactobacillus and Bifidobacterium genera. In this field, personal beliefs, intuition, and commercial interests, coupled with a lack of sufficient medical regulation, often combine to make objective interpretation difficult [The most common intervention is the intake of a beneficial microorganism probiotic and/or prebiotic, but a wider discussion of the evidence of the beneficial effects is ongoing . The maiifficult . On the ifficult .The most acceptable intervention consists of a variation in nutritional behavior, which can shift the microbiota characteristics and lead to an improvement in the balance of the gut microbiota by increasing health-favoring bacteria. A valuable effect is observable in the medium and long term, but only for as long as the subject maintains the healthy diet .Bifidobacteriaceae, Faecalibacterium spp., Ruminococcaceae, Dialister, Roseburia, and Akkermansia. On the other hand, an increase of Prevotella and Enterococcus leads to greater risk , but, today, a consolidation of the evidence is needed as a cost-efficacy evaluation. Moreover, a cohort study with long observation during childhood can elucidate the real contribution of microbiota variation. Precision medicine, also known as personalized or stratified medicine, is an emerging paradigm in disease diagnosis, prevention, and treatment ,132, aimIn a multisystemic disease process such as an infection, blood (serum and plasma) analysis provides early detection to characterize the damage, with the use of molecular technologies revealing specific biomarkers associated with certain phenotypes/trait groups, leading to therapeutic changes in patients with diverse clinical presentations . Indeed,Since the beginning of 2020, the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly led to serious challenges for hospital care , and corDespite the majority of individuals with COVID-19 exhibiting only mild symptoms or even being asymptomatic, there are patients who develop serious complications, underlining the fact that it is crucial to identify who is at higher risk of a worse prognosis and to recognize reliable outcome predictors in a timely manner for improving patient management. As a result, the personalized medicine approach appears to be highly appropriate for the study of COVID-19, considering the wide spectrum of severity and variable phenotypes , includiThere is growing evidence that COVID-19 occurs more in males ,154, theTo date, research focused on the analysis of single-nucleotide polymorphisms (SNPs) of the angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, revealed that morbidity, clinical course, and mortality depend on ACE D allele frequency . AnotherIn a study, RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive patients with diverse severity profiles and negative individuals were used to quantify transcripts, proteins, metabolites, and lipids in a relational database, enabling analysis and correlations between molecules and patient prognoses. A total of 219 molecular features were mapped with high significance for severity, mainly involved into complement activation, dysregulated lipid transport, and neutrophil activation .As COVID-19 is characterized by a variable course, with asymptomatic individuals and others experiencing fever, ARDS, or even death, understanding of the antibody response in subjects with severe compared to mild disease is needed. A high-throughput method was used to analyze epitopes of antiviral antibodies in human sera of 232 COVID-19 patients and 190 controls. Results highlighted epitopes ranging from “private”, recognized by antibodies in only a small number of subjects, to “public”, recognized by antibodies in many individuals, and those with severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, as well as weaker antibody responses to prior infections . In conclusion, considering the rapid evolution of the current epidemiological situation and the need to ensure adequate continuity of care and contain transmission, precision medicine is the key to fighting the COVID-19 pandemic by creating patient-specific treatment programs tailored to individual needs. This novel approach, implying the integration of clinical, lifestyle, genetic, and biomarker information for patient stratification, could enable us to achieve a better understanding of critical disease pathways and more precise and validated phenotypic recognition. Multi-omics systems could provide critical information to better understand SARS-CoV-2 and COVID-19 features, defining the individual genetic predisposition for both infection and course severity. For example, epigenomic and transcriptomic analyses would allow us to characterize changes in tissues involved in COVID-19, and to understand the interaction between SARS-CoV-2 and patient cells as a reaction to viral infection. Data integration would finally enable the identification of biomarkers and therapeutic targets to stratify patients and allow better interventions and decisions. Hence, an understanding of pathogenic pathways and the classification of phenotypes in SARS-CoV-2-infected patients might significantly contribute to the design of effective prevention strategies, mitigation interventions, and personalized pharmacological options in order to guide public health actions and improve the chances of better outcomes.The existing evaluation frameworks for genetic tests, and genetic/genomic applications in general, mainly rely on two popular evaluation approaches, i.e., the ACCE model  and the Health Technology Assessment (HTA) process . The U.SUnlike the ACCE model, the HTA approach was developed to cover all health technologies. However, since its creation in the USA in the late 1960s, some attempts have been made to adjust it for the evaluation of genetic tests. A notable example is a framework proposed to guide the public coverage of new predictive genetic tests in Ontario, Canada, which proposed the following criteria to assess a genetic test: intended purpose, effectiveness, additional effects, aggregate costs, demand, and cost-effectiveness ,178. TheBased on these findings, a combination of the ACCE model, with its focus on the unique aspects characterizing the genetic tests, and the HTA process, useful to guide provision and coverage decisions, might represent the best approach to the evaluation of genetic tests. Recently, Sapienza University of Rome tried to realize such an integrated approach and proposed a framework distinguished by a dual focus on both the genetic test and its delivery models . The firOverall, despite the efforts made, several issues still affect the evaluation of genetic/genomic applications. The first one, mainly related to the delivery model approach, is the generalizability of findings, given the context-dependence of economic and organizational issues. Another challenge is the lack of scientific evidence to use for evaluation, especially translation studies . FinallyOmics sciences can be considered as disruptive innovations that promise a new era of precision health (PH). To fully harness such potential, we envisage some key prerequisites linked to the system’ capacity building: (i) health professionals should be enabled to manage the omics knowledge and applications, and (ii) citizens need to gain sufficient health literacy to understand the potential benefits, limits, and risks of omics technologies concerning their health . While several European countries have implemented specific health policies in this field, few countries have integrated public health genomics into the health system offerings , e.g., ISuccessful personalized healthcare will only be achieved; however, if all stakeholders develop the required awareness of PH, and this can be achieved by improving health professionals’ capacity building and citizens’ literacy.The integration of the omics innovation into health system policy and practice requires highly engaged and appropriately trained health professionals . A lack https://www.eduiss.it/) [In Italy, several initiatives were implemented with the aim of achieving better genomics literacy for both health professionals and the general public. Such educational efforts are in line with the goals of the Italian National Innovation Plan of the Healthcare System, based on omics sciences and published in 2017 . Since 2iss.it/) .With the rapid advances in omics technologies, the demand for well-trained healthcare professionals will grow exponentially, and omics education will need to evolve to keep up with the changing scientific landscape. Therefore, for effective and successful implementation of PH, improving health professionals’ literacy will need to be a priority, along with suitable common principles, appropriate policies, and regulatory frameworks. Among the great challenges that should be addressed to allow for the correct implementation and integration of omics sciences into healthcare practice, citizens’ engagement and literacy will play a key role . CitizenA striking example of the potential impact of omics technologies on citizens’ health and healthcare systems is direct-to-consumer genetic tests (DTC-GTs). The increasing demand for DTC-GTs among laypeople, together with their peculiar provisional model—i.e., not requiring counseling by health professionals—need not only a careful analysis of the potential benefits and risks by policy-makers , but alsThis further underlines the importance of citizen engagement and literacy in this field, which would allow them to adopt a more active role in the protection of their own health and in shaping more effective strategies for the implementation of personalized healthcare .Several strategic actions will need to be taken to allow for the easy integration of omics knowledge and technologies into healthcare .developing awareness among stakeholders;improving citizens’ health literacy to fully empower them;fostering health professionals’ skills acquisition through extensive educational initiatives in omics sciences;shaping sustainable healthcare through the use of evidence-based tools such as a Health Technology Assessment for the omics technologies’ evaluation to introduce in healthcare systems.We could envisage among the main actions: The Departments of Prevention (DP) are parts of the Local Units of the Italian National Health Service, which oversee public health activities. Their main duties are health promotion, disease prevention, livestock and pet health, and food safety. They promote public well-being by promoting healthy behaviors, preventing infectious and chronic diseases, and improving work safety. They are involved in the strategic planning and evaluation of preventive programs as essential ways to achieve health-related goals. The Direction of the DP guarantees comprehensive governance and integration among the different activity areas and is expected to coordinate and organize public health initiatives .The National Prevention Plan (NPP) it subdivided into regional and local prevention plans, which play a key role in the governance of public health programs. There are some characteristics that public health programs have in common: theyare addressed to healthy people in large numbers;represent “proactive” medicine;provide cost-effective and evidence-based technologies;deliver free or co-payment health care services;consider individual as well as community health gain; andare provided in all regions of Italy, as they are mandatory.cancer screeningsvaccination campaignsrisk communication, counseling, health literacy, and empowerment of the target populationepidemiological evaluation of the health efficacy in the target populationhealth surveillance activityinfectious disease These programs are implemented in the following fields:must be efficacy- and value-based;needs dedicated resources ;needs a structured plan from prevention to treatment;must avoid inequalities; andrequires people’s advocacy and involvement.In general, a public health intervention: The same fundamental principles can also be applied to the field of “predictive medicine”, which, in the public health sector, can be implemented by the DP . Predictgenerating more specific and cost-effective public prevention programs;enhancing the impact of prevention and risk-reduction campaigns;favoring the exchange of information between various branches of the public health sector; andmaintaining the importance of a central public health author even if the trend is toward personalized medicine.The integration of genomics into public health should achieve these results:The NPP 2010–2012 underlined the importance of predictive medicine and its huge potential to identify a population of healthy individuals who are at risk of developing specific diseases . This coTherefore, it is necessary to enhance the understanding of predictive medicine and how it can be developed by the DP. Discussion and implementation have just started. To date, predictive medicine has only found a few applications in Italy. Genomic predictive tests are used in public health settings only to investigate monogenic disorders. These include screening for high-penetrance mutations such as breast, ovarian, and colorectal cancer. Genetic screening for complex diseases has been applied to a very limited number of conditions. For example, the NPP 2014‒2018, based on the public health genomics approach, aimed to develop organized paths of breast cancer prevention in women with BRCA1/2 mutations [On the other hand, large-scale prevention programs that target large population groups  are already part of the system and have been used for several years. They can constitute essential background to the introduction of predictive medicine in routine activities of DP .consolidated and experienced activity of screening;an existing network with clinical disciplines;experience of risk communication and counseling;experience of follow-up management;an appropriate attitude toward the analysis and evaluation of prevention activities;appropriate software in use.There are many reasons to think that the role of the DP could be central and appropriate:In conclusion, predictive medicine in the context of cancer screening is already feasible, but it would require an adaptive process to enhance the knowledge and practical organization. DP healthcare workers will have to increase their specific competences. However, these are often already used in daily activities like screening and health promotion, but should be updated with genomics knowledge. On the other hand, vaccine activities may also profit from genomic screening by taking advantage of the stratification of populations and the identification of nonresponders based on their genetic profile. Additionally, the recent COVID-19 epidemic might open up new uses for predictive medicine to identify individuals at high risk of developing a severe condition.Plan for innovations in the health system based on omics sciences” (published in 2018) defined ways to improve the health system through the application of omics science [The “ science . This in science .The omics sciences offer a wide range of tools to improve public health: from a single polymorphism detection to the PGS approach, and including whole-genome and exosome sequencing. The interaction between a gene and the environment can be defined by the epigenetic end-point and also by the evaluation of the microbiome shift from eubiosis to dysbiosis, highlighting several prevention opportunities, especially for the early detection of diseases or at-risk conditions. However, the introduction and accessibility of such tools are not yet guaranteed in Italy and they are provided by private bodies, individuals, and sporadic ventures. In the future, disease prevention and treatment should be formulated at the individual level according to genomic features. However, a current major challenge is a lack or scarcity of scientific evidence, as well as a lack of ethical, legal, and social regulations. The implementation of omics advancements into clinical practice depends on countries’ ability to adopt relevant strategies and innovative approaches. The production, integration, and use of genetic/genomic information in healthcare require significant changes in the way such care is organized and provided to individuals. This is also evident in relation to the COVID-19 pandemic. Therefore, new health policies and specific programs on the omics sciences will be needed to respond to the needs of citizens and all health stakeholders.