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PubMed2026

Osteoarthritis Year in Review 2026: Genetics, genomics and epigenetics.

OBJECTIVE: The purpose of this narrative review is to highlight advances made over the past 12 months in the field of osteoarthritis (OA) genetics, genomics and epigenomics, with a particular focus on the interpretation of OA risk loci through functional genomic and regulatory approaches. DESIGN: PubMed and Europe PMC were searched to identify studies relevant to OA genetics, genomics and epigenomics published between 1st March 2025 and 30th April 2026. Searches used combinations of terms relating to genetics, genomics, epigenomics, functional genomics, molecular quantitative trait loci, chromatin accessibility and enhancer biology. Studies were limited to human subjects and English-language publications, with additional articles identified through citation screening and expert knowledge of the field. RESULTS: Over the past year, the field has continued to transition from large-scale locus discovery towards biological interpretation of OA genetic risk. Major advances included the largest OA genome-wide association study to date, further development of polygenic risk score approaches, and increasing integration of molecular quantitative trait loci, chromatin accessibility, and enhancer biology datasets to prioritise effector genes and elucidate regulatory mechanisms. Several studies highlighted the highly context-dependent nature of OA genetic risk mechanisms, demonstrating that distinct tissues, cell types, and regulatory layers can identify different candidate effector genes at the same locus. Additional developments included increasing application of singlecell and multi-omic technologies to study OA-relevant tissues. CONCLUSION: Recent advances in OA genetics have shifted the field from locus discovery towards mechanistic interpretation. Emerging evidence demonstrates that the biological consequences of genetic variation are highly dependent upon tissue, cell state and disease context, with different functional genomic approaches often prioritising distinct candidate genes and regulatory mechanisms at the same susceptibility locus. Together, these findings suggest that OA risk loci should increasingly be viewed as dynamic regulatory systems rather than simple variant-to-gene relationships, providing a framework for future studies aimed at resolving causal mechanisms, defining disease endotypes, and identifying therapeutic targets.

Genetics↗
PubMed2002

Deductive genomics: a functional approach to identify innovative drug targets in the post-genome era.

The sequencing of the human genome has generated a drug discovery process that is based on sequence analysis and hypothesis-driven (inductive) prediction of gene function. This approach, which we term inductive genomics, is currently dominating the efforts of the pharmaceutical industry to identify new drug targets. According to recent studies, this sequence-driven discovery process is paradoxically increasing the average cost of drug development, thus falling short of the promise of the Human Genome Project to simplify the creation of much needed novel therapeutics. In the early stages of discovery, the flurry of new gene sequences makes it difficult to pick and prioritize the most promising product candidates for product development, as with existing technologies important decisions have to be based on circumstantial evidence that does not strongly predict therapeutic potential. This is because the physiological function of a potential target cannot be predicted by gene sequence analysis and in vitro technologies alone. In contrast, deductive genomics, or large-scale forward genetics, bridges the gap between sequence and function by providing a function-driven in vivo screen of a highly orthologous mammalian model genome for medically relevant physiological functions and drug targets. This approach allows drug discovery to move beyond the focus on sequence-driven identification of new members of classical drug-able protein families towards the biology-driven identification of innovative targets and biological pathways.

Animals↗
PubMed2000

An infrastructure for comparative genomics to functionally characterize genes and proteins.

Current genome projects are resulting in a flood of sequence data. The interpretation of these sequences is lagging, and optimized data analysis strategies need to be developed. Much can be learned from comparing different genomes, as genomes of distant organisms may still encode proteins with high sequence similarity. The order of genes (co linearity) in genomes may also be conserved to some extend. We have employed both these observations to create a multi-functional, computational analysis system (genomeSCOUT) which allows for rapid identification and functional characterization of genes and proteins through genome comparison. With a number of independent algorithms, information about different levels of protein homology (concerning e.g. paralogs, orthologs and clusters of orthologous groups, COGs) and gene order is collected and stored in several value added databases. These databases are then used for interactive comparison of genomes and subsequent analysis. The application is based on the well established data integration system SRS. This ensures (1) fast handling of large genomic data sets, (2) straightforward access to a multitude of biological databases, (3) unique linking functions between these databases, (4) highly efficient collection of information on genes and proteins, and 5. fully integrated and user friendly graphical representations of search results. This application can be used for projects as diverse as the correct annotation of genomes, the optimization of (micro) organisms for industrial production, or the identification of drug targets.

Computational Biology↗
PubMed2001

[Is disease grounded in the mind, the spirit or communication? Pathology as a leading path in learning about disease].

What is the reason, why pathology could command a dominating position as a central teaching discipline in the last 150 years? Furthermore: can this position be maintained in the future? Pathology takes its definitive stand in the philosophic confrontation of "Mind" versus "Matter". It guards the dogma of Morgagni: every disease is reflected by its typical morphological substrate. As long as this dogma is guarded and defended by the discipline of pathology, we will stay at the helm of teaching in medicine. Recently information as a third reality (besides mind and matter) has come into existence. Information is defined here as genomic information specifically the differentially activated functional genomics. In extension to the old dogma of Morgagni we recognize now an extension to "functional" diseases where we do not (yet) find a pathological anatomical manifestation. In these cases "information" is defined as differences in physical states. They can be converted to information in the sense of meaning and purpose by communication. Pathology provides the bridge between functional genomics and morphological manifestations of diseases (phenomics). The future of pathology is based on the amalgamation of the old and reliable Morgagni-Virchow dogma with the new informational dogma. If pathology provides sense, meaning and significance to phenomics, morphology in relation to functional genomics it will retain and even enlarge its influence as the most important teaching discipline in medicine.

Communication↗
PubMed2002

Gene networks: how to put the function in genomics.

An increasingly popular model of regulation is to represent networks of genes as if they directly affect each other. Although such gene networks are phenomenological because they do not explicitly represent the proteins and metabolites that mediate cell interactions, they are a logical way of describing phenomena observed with transcription profiling, such as those that occur with popular microarray technology. The ability to create gene networks from experimental data and use them to reason about their dynamics and design principles will increase our understanding of cellular function. We propose that gene networks are also a good way to describe function unequivocally, and that they could be used for genome functional annotation. Here, we review some of the concepts and methods associated with gene networks, with emphasis on their construction based on experimental data.

Animals↗
PubMed2002

Developmental genomic approaches in model organisms.

Functional genomics technologies can help decipher how information encoded in the genome is translated into morphology, physiology, and behavior during the development of complex organisms. A number of researchers have begun to apply DNA microarrays and other functional genomics approaches to study development. Here we review recent studies that take the first steps toward relating genome-wide information to developmental events, we discuss recent genomics approaches taken in animal model systems used to study human disease, and we outline methods that may be useful for constructing genome-wide maps of developmental processes.

Animals↗
PubMed2005

Syntons, metabolons and interactons: an exact graph-theoretical approach for exploring neighbourhood between genomic and functional data.

MOTIVATION: Modern comparative genomics does not restrict to sequence but involves the comparison of metabolic pathways or protein-protein interactions as well. Central in this approach is the concept of neighbourhood between entities (genes, proteins, chemical compounds). Therefore there is a growing need for new methods aiming at merging the connectivity information from different biological sources in order to infer functional coupling. RESULTS: We present a generic approach to merge the information from two or more graphs representing biological data. The method is based on two concepts. The first one, the correspondence multigraph, precisely defines how correspondence is performed between the primary data-graphs. The second one, the common connected components, defines which property of the multigraph is searched for. Although this problem has already been informally stated in the past few years, we give here a formal and general statement together with an exact algorithm to solve it. AVAILABILITY: The algorithm presented in this paper has been implemented in C. Source code is freely available for download at: http://www.inrialpes.fr/helix/people/viari/cccpart.

Algorithms↗
PubMed2026

Expanding the scope of precision editing in seaweeds through the application of a novel CRISPR-associated nuclease 12a-aligned CRISPR system in Ulva prolifera.

Seaweeds, such as the fast-growing green alga Ulva prolifera, can be harnessed as valuable marine crops. The lack of scalable genome-editing tools hampers functional genomics to explore and elucidate algal molecular pathways with industrial importance. Here, we expanded precision genome modification in seaweeds by successfully demonstrating gene editing with a transgene-free AT-rich-targeting CRISPR-associated protein (Cas) system in U. prolifera. By evaluating various delivery buffers, comparing different Cas systems, and optimizing incubation temperatures, we determined suitable conditions for more widespread applicability of a novel Cas12a-aligned ST8 editor. We obtained >50 ST8-mediated knockout mutants of a toxin-based endogenous marker gene, UpAPT, at 28 °C post-delivery incubations. Our work diversified the applicable genome-editing tools in seaweeds, advancing algal functional genomics and providing more strategies to precisely target unexplored seaweed resources.

Ulva↗
PubMed2006

Ancient duplicated conserved noncoding elements in vertebrates: a genomic and functional analysis.

Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development. Although most of these elements share little sequence identity to each other, a small number are remarkably similar and appear to be the product of duplication events. Here, we searched for duplicated conserved noncoding elements in the human genome, using comparisons with Fugu to select putative cis-regulatory sequences. We identified 124 families of duplicated elements, each containing between two and five members, that are highly conserved within and between vertebrate genomes. In 74% of cases, we were able to assign a specific set of paralogous genes with annotation relating to transcriptional regulation and/or development to each family, thus removing much of the ambiguity in identifying associated genes. We find that duplicate elements have the potential to up-regulate reporter gene expression in a tissue-specific manner and that expression domains often overlap, but are not necessarily identical, between family members. Over two thirds of the families are conserved in duplicate in fish and appear to predate the large-scale duplication events thought to have occurred at the origin of vertebrates. We propose a model whereby gene duplication and the evolution of cis-regulatory elements can be considered in the context of increased morphological diversity and the emergence of the modern vertebrate body plan.

Animals↗
PubMed2002

Genome organization and reorganization in evolution: formatting for computation and function.

This volume deals with the role of epigenetics in life and evolution. The most dynamic forms of functional genome formatting involve DNA interacting with cellular complexes that do not alter sequence information. Such important epigenetic phenomena are the main subjects of other articles in this volume. This article focuses on the long-lived form of genome formatting that lies within the DNA sequence itself. I argue for a computational view of genome function as the long-term information storage organelle of each cell. Structural formatting consists of organizing various signals and coding sequences into computationally ready systems facilitating genome expression and genome transmission. The basic features of genome organization can be understood by examining the E. coli lac operon as a paradigmatic genomic system. Multiple systems are connected through distributed signals and repetitive DNA to form higher-order genome system architectures. Molecular discoveries about mechanisms of DNA restructuring show that cells possess the natural genetic engineering functions necessary for evolutionary change by rearranging genomic components and reorganizing system architectures. The concepts of cellular computation and decision-making, genome system architecture, and natural genetic engineering combine to provide a new way of framing evolutionary theories and understanding genome sequence information.

Animals↗
PubMed2002

Functional and genomic implications of global gene expression profiles in cell lines from human hepatocellular cancer.

Global gene expression profiles in cancer have impacted both classification of tumors and definition of molecular pathways in neoplasia. To explore the possibility of employing human tumor cell lines to obtain information on the functional genomics of the early stages of tumorigenesis, we have characterized variation in gene-expression patterns in a cytogenetically well-defined series of cell lines derived from human hepatocellular carcinoma (HCC). Microarrays containing 6,720 sequence-verified human cDNAs were used in this study. Nineteen well-characterized HCC cell lines were analyzed, and a nontumorigenic liver-derived epithelial cell line (Chang) was used as a reference. Each sample was examined at least twice by switching fluorescent dyes, Cy-5 and Cy-3, and average values of 2 experiments on each sample were used for further analysis. Analysis of the clustered data revealed 2 distinctive subtypes of gene-expression patterns among the 19 cell lines, suggesting a degree of heterogeneity among the gene-expression profiles of cell lines. Remarkably, expression of alpha-fetoprotein (AFP) was highly correlated with the molecular subtypes of HCC. Although the 3 most distinctive gene-expression modules represented the signatures of 2 different subgroups of HCC, most of the cell lines shared many coexpressed genes. However, sets of coexpressed genes that are specific for the subtypes of HCC were identified. Furthermore, our results indicate that the comparison between gene-expression patterns and structural alterations in chromosomes is potentially useful in identifying genes critical in early stages of tumorigenesis. In conclusion, these results not only identified unrecognized subtypes of HCC, but also provided potential molecular markers for each subtype that can be useful for diagnostic and/or therapeutic purposes.

Carcinoma, Hepatocellular↗
PubMed2002

Genomics of Helicobacter pylori.

During this review period, we have definitely entered into the genomic era. The Helicobacter pylori studies reported here illustrate the use of most of the technologies currently available to globally interrogate the genome of a pathogen. Global analysis of the gene content of H. pylori strains gives insight into the extent of its genetic diversity and its in vivo evolution. Our understanding of the particularities of H. pylori as a gastric pathogen colonizing a unique niche has been improved by studies aimed at: (i) the identification of H. pylori-specific genes; (ii) the establishment of correlations between the presence of one or a group of genes (or proteins) with clinical outcome; and (iii) the analysis of global regulatory circuits or responses to the extracellular signals. The response of host cells to H. pylori infection will be developed in the chapter 'H. pylori and gastric malignancies' by Sepulveda and Coehlo. Despite our knowledge of the H. pylori genome, the function of about one third of its total proteins is still unknown. Functional genomics are straightforward approaches for the identification of new gene functions or metabolic pathways as well as for the understanding of cellular processes and the detection of new virulence factors. In silico studies combined with experimental work will undoubtedly continue to develop. To date, the expansion of proteomics with refinements in mass spectrometry technology has illustrated that through immunoproteomics and comparative studies, relevant novel antigens can be identified. Genomics not only provides invaluable information on H. pylori but also opens new perspectives for diagnostic or therapeutic applications.

Genome, Bacterial↗
PubMed2003

Development and testing of a high-density cDNA microarray resource for cattle.

A cDNA microarray resource has been developed with the goal of providing integrated functional genomics resources for cattle. The National Bovine Functional Genomics Consortium's (NBFGC) expressed sequence tag (EST) collection was established in 2001 to develop resources for functional genomics research. The NBFGC EST collection and microarray contains 18,263 unique transcripts, derived from many different tissue types and various physiologically important states within these tissues. The NBFGC microarray has been tested for false-positive rates using self-self hybridizations and was shown to yield robust results in test microarray experiments. A web-accessible database has been established to provide pertinent data related to NBFGC clones, including sequence data, BLAST results, and ontology information. The NBFGC microarray represents the largest cDNA microarray for a livestock species prepared to date and should prove to be a valuable tool in studying genome-wide gene expression in cattle.

Animals↗
PubMed2003

The function of genomes in bioenergetic organelles.

Mitochondria and chloroplasts are energy-transducing organelles of the cytoplasm of eukaryotic cells. They originated as bacterial symbionts whose host cells acquired respiration from the precursor of the mitochondrion, and oxygenic photosynthesis from the precursor of the chloroplast. The host cells also acquired genetic information from their symbionts, eventually incorporating much of it into their own genomes. Genes of the eukaryotic cell nucleus now encode most mitochondrial and chloroplast proteins. Genes are copied and moved between cellular compartments with relative ease, and there is no obvious obstacle to successful import of any protein precursor from the cytosol. So why are any genes at all retained in cytoplasmic organelles? One proposal is that these small but functional genomes provide a location for genes that is close to, and in the same compartment as, their gene products. This co-location facilitates rapid and direct regulatory coupling. Redox control of synthesis de novo is put forward as the common property of those proteins that must be encoded and synthesized within mitochondria and chloroplasts. This testable hypothesis is termed CORR, for co-location for redox regulation. Principles, predictions and consequences of CORR are examined in the context of competing hypotheses and current evidence.

Chloroplasts↗
PubMed1996

From DNA sequence to biological function.

Genome sequencing is leading to the discovery of new genes at a rate 50-100 times greater than that achieved by classical genetics, but the biological function of almost half of these genes is completely unknown. In order fully to exploit genome sequence data, a systematic approach to the discovery of gene function is required. Possible strategies are discussed here in the context of functional analysis in the yeast Saccharomyces cerevisiae, a model eukaryote whose genome sequence will soon be completed.

Base Sequence↗
PubMed2005

A dual selection based, targeted gene replacement tool for Magnaporthe grisea and Fusarium oxysporum.

Rapid progress in fungal genome sequencing presents many new opportunities for functional genomic analysis of fungal biology through the systematic mutagenesis of the genes identified through sequencing. However, the lack of efficient tools for targeted gene replacement is a limiting factor for fungal functional genomics, as it often necessitates the screening of a large number of transformants to identify the desired mutant. We developed an efficient method of gene replacement and evaluated factors affecting the efficiency of this method using two plant pathogenic fungi, Magnaporthe grisea and Fusarium oxysporum. This method is based on Agrobacterium tumefaciens-mediated transformation with a mutant allele of the target gene flanked by the herpes simplex virus thymidine kinase (HSVtk) gene as a conditional negative selection marker against ectopic transformants. The HSVtk gene product converts 5-fluoro-2'-deoxyuridine to a compound toxic to diverse fungi. Because ectopic transformants express HSVtk, while gene replacement mutants lack HSVtk, growing transformants on a medium amended with 5-fluoro-2'-deoxyuridine facilitates the identification of targeted mutants by counter-selecting against ectopic transformants. In addition to M. grisea and F. oxysporum, the method and associated vectors are likely to be applicable to manipulating genes in a broad spectrum of fungi, thus potentially serving as an efficient, universal functional genomic tool for harnessing the growing body of fungal genome sequence data to study fungal biology.

Agrobacterium tumefaciens↗
PubMed2004

Molecular therapeutics: promise and challenges.

The ability to analyze the genetic and epigenetic aberrations present in a particular patient's tumor on a global basis is rapidly maturing. The emerging fields of functional genomics and functional proteomics offer the opportunity to translate these advances into a full comprehension of the pathophysiology of cancer. Linking these approaches to chemical genomics and molecular therapeutics should provide an expanding repertoire of targeted therapeutics for clinical evaluation. Novel clinical trial designs that can determine the efficacy of targeted therapeutics in patients selected for aberrations in the target are needed to evaluate the wealth of new drugs becoming available. The promise of these technologies and advances in our understanding of cancer is immense, making it our responsibility to see them to fruition. These technologies should lead to a new era of individualized molecular medicine, wherein we will treat each patient with a "prescription" based on the genetic changes in each patient's tumor and their own genetic make-up, resulting in more effective and less toxic therapy.

Animals↗
PubMed2006

Bioinformatics methods for identifying candidate disease genes.

With the explosion in genomic and functional genomics information, methods for disease gene identification are rapidly evolving. Databases are now essential to the process of selecting candidate disease genes. Combining positional information with disease characteristics and functional information is the usual strategy by which candidate disease genes are selected. Enrichment for candidate disease genes, however, depends on the skills of the operating researcher. Over the past few years, a number of bioinformatics methods that enrich for the most likely candidate disease genes have been developed. Such in silico prioritisation methods may further improve by completion of datasets, by development of standardised ontologies across databases and species and, ultimately, by the integration of different strategies.

Computational Biology↗