1. |
- Altenhoff, Adrian M., et al.
(author)
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Standardized benchmarking in the quest for orthologs
- 2016
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In: Nature Methods. - 1548-7091 .- 1548-7105. ; 13:5, s. 425-
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Journal article (peer-reviewed)abstract
- Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.
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2. |
- Aydın, Efe, et al.
(author)
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A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer
- 2023
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In: IUBMB Life. - : Wiley. - 1521-6543 .- 1521-6551. ; 75:7, s. 566-579
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Journal article (peer-reviewed)abstract
- Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A > G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation alters NEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of several NEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation of Vimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.
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3. |
- Dessimoz, Christophe, et al.
(author)
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Toward community standards in the quest for orthologs
- 2012
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 28:6, s. 900-904
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Journal article (other academic/artistic)abstract
- The identification of orthologs-genes pairs descended from a common ancestor through speciation, rather than duplication-has emerged as an essential component of many bioinformatics applications, ranging from the annotation of new genomes to experimental target prioritization. Yet, the development and application of orthology inference methods is hampered by the lack of consensus on source proteomes, file formats and benchmarks. The second 'Quest for Orthologs' meeting brought together stakeholders from various communities to address these challenges. We report on achievements and outcomes of this meeting, focusing on topics of particular relevance to the research community at large. The Quest for Orthologs consortium is an open community that welcomes contributions from all researchers interested in orthology research and applications.
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4. |
- du Toit, Lisa, et al.
(author)
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The Effect of Dietary Nitrate on the Oral Microbiome and Salivary Biomarkers in Individuals with High Blood Pressure.
- 2024
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In: Journal of Nutrition. - : Elsevier. - 0022-3166 .- 1541-6100.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Green leafy vegetables (GLV) contain inorganic nitrate, an anion with potential prebiotic effects on the oral microbiome. However, it remains unclear whether GLV and pharmacological supplementation [potassium nitrate (PN)] with a nitrate salt induce similar effects on the oral microbiome.OBJECTIVES: This study aimed to compare the effect of GLV with PN supplementation on the oral microbiome composition and salivary biomarkers in individuals with high blood pressure.METHODS: Seventy individuals were randomly allocated to 3 different groups to follow a 5-wk dietary intervention. Group 1 consumed 300 mg/d of nitrate in form of GLV. Group 2 consumed pills with 300 mg/d of PN and low-nitrate vegetables. Group 3 consumed pills with potassium chloride (placebo: PLAC) and low-nitrate vegetables. The oral microbiome composition and salivary biomarkers of oral health were analyzed before and after the dietary intervention.RESULTS: The GLV and PN groups showed similar microbial changes, probably nitrate-dependent, including an increase in the abundance of Neisseria, Capnocytophaga, Campylobacter species, and a decrease in Veillonella, Megasphaera, Actinomyces, and Eubacterium species after the treatment. Increased abundance of Rothia species, and reduced abundance of Streptococcus, Prevotella, Actinomyces, and Mogibacterium species were observed in the GLV group, which could be nitrate-independent. GLV and PN treatments increased salivary pH, but only GLV treatment showed an increase in the salivary buffering capacity and a reduction of lactate.CONCLUSION: The combination of nitrate-dependent and nitrate-independent microbial changes in the GLV group has a stronger effect to potentially improve oral health biomarkers compared with PN.
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5. |
- Forslund, Kristoffer, et al.
(author)
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Gearing up to handle the mosaic nature of life in the quest for orthologs
- 2018
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 34:2, s. 323-329
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Journal article (peer-reviewed)abstract
- The Quest for Orthologs (QfO) is an open collaboration framework for experts in comparative phylogenomics and related research areas who have an interest in highly accurate orthology predictions and their applications. We here report highlights and discussion points from the QfO meeting 2015 held in Barcelona. Achievements in recent years have established a basis to support developments for improved orthology prediction and to explore new approaches. Central to the QfO effort is proper benchmarking of methods and services, as well as design of standardized datasets and standardized formats to allow sharing and comparison of results. Simultaneously, analysis pipelines have been improved, evaluated and adapted to handle large datasets. All this would not have occurred without the long-term collaboration of Consortium members. Meeting regularly to review and coordinate complementary activities from a broad spectrum of innovative researchers clearly benefits the community. Highlights of the meeting include addressing sources of and legitimacy of disagreements between orthology calls, the context dependency of orthology definitions, special challenges encountered when analyzing very anciently rooted orthologies, orthology in the light of whole-genome duplications, and the concept of orthologous versus paralogous relationships at different levels, including domain-level orthology. Furthermore, particular needs for different applications (e.g. plant genomics, ancient gene families and others) and the infrastructure for making orthology inferences available (e.g. interfaces with model organism databases) were discussed, with several ongoing efforts that are expected to be reported on during the upcoming 2017 QfO meeting.
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6. |
- Gabaldón, Toni, et al.
(author)
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Joining forces in the quest for orthologs
- 2009
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In: Genome biology. - : Springer Science and Business Media LLC. - 1465-6914 .- 1465-6906. ; 10:9, s. 403-
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Journal article (peer-reviewed)abstract
- Better orthology-prediction resources would be beneficial for the whole biological community. A recent meeting discussed how to coordinate and leverage current efforts.
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7. |
- Gerardo, Nicole M, et al.
(author)
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Immunity and other defenses in pea aphids, Acyrthosiphon pisum.
- 2010
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 11:2
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites and stresses. At the center of pathogen-induced immune responses are signaling pathways triggered by the recognition of fungal, bacterial and viral signatures. These pathways result in the production of response molecules, such as antimicrobial peptides and lysozymes, which degrade or destroy invaders. Using the recently sequenced genome of the pea aphid (Acyrthosiphon pisum), we conducted the first extensive annotation of the immune and stress gene repertoire of a hemipterous insect, which is phylogenetically distantly related to previously characterized insects models.RESULTS: Strikingly, pea aphids appear to be missing genes present in insect genomes characterized to date and thought critical for recognition, signaling and killing of microbes. In line with results of gene annotation, experimental analyses designed to characterize immune response through the isolation of RNA transcripts and proteins from immune-challenged pea aphids uncovered few immune-related products. Gene expression studies, however, indicated some expression of immune and stress-related genes.CONCLUSIONS: The absence of genes suspected to be essential for the insect immune response suggests that the traditional view of insect immunity may not be as broadly applicable as once thought. The limitations of the aphid immune system may be representative of a broad range of insects, or may be aphid specific. We suggest that several aspects of the aphid life style, such as their association with microbial symbionts, could facilitate survival without strong immune protection.
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8. |
- Glover, Natasha, et al.
(author)
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Advances and Applications in the Quest for Orthologs
- 2019
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 36:10, s. 2157-2164
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Research review (peer-reviewed)abstract
- Gene families evolve by the processes of speciation (creating orthologs), gene duplication (paralogs), and horizontal gene transfer (xenologs), in addition to sequence divergence and gene loss. Orthologs in particular play an essential role in comparative genomics and phylogenomic analyses. With the continued sequencing of organisms across the tree of life, the data are available to reconstruct the unique evolutionary histories of tens of thousands of gene families. Accurate reconstruction of these histories, however, is a challenging computational problem, and the focus of the Quest for Orthologs Consortium. We review the recent advances and outstanding challenges in this field, as revealed at a symposium and meeting held at the University of Southern California in 2017. Key advances have been made both at the level of orthology algorithm development and with respect to coordination across the community of algorithm developers and orthology end-users. Applications spanned a broad range, including gene function prediction, phylostratigraphy, genome evolution, and phylogenomics. The meetings highlighted the increasing use of meta-analyses integrating results from multiple different algorithms, and discussed ongoing challenges in orthology inference as well as the next steps toward improvement and integration of orthology resources.
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9. |
- Green, Richard E., et al.
(author)
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Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
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Journal article (peer-reviewed)abstract
- To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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10. |
- Jarvis, Erich D., et al.
(author)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Journal article (peer-reviewed)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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11. |
- Linard, Benjamin, et al.
(author)
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Ten Years of Collaborative Progress in the Quest for Orthologs
- 2021
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:8, s. 3033-3045
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Research review (peer-reviewed)abstract
- Accurate determination of the evolutionary relationships between genes is a foundational challenge in biology. Homology-evolutionary relatedness-is in many cases readily determined based on sequence similarity analysis. By contrast, whether or not two genes directly descended from a common ancestor by a speciation event (orthologs) or duplication event (paralogs) is more challenging, yet provides critical information on the history of a gene. Since 2009, this task has been the focus of the Quest for Orthologs (QFO) Consortium. The sixth QFO meeting took place in Okazaki, Japan in conjunction with the 67th National Institute for Basic Biology conference. Here, we report recent advances, applications, and oncoming challenges that were discussed during the conference. Steady progress has been made toward standardization and scalability of new and existing tools. A feature of the conference was the presentation of a panel of accessible tools for phylogenetic profiling and several developments to bring orthology beyond the gene unit-from domains to networks. This meeting brought into light several challenges to come: leveraging orthology computations to get the most of the incoming avalanche of genomic data, integrating orthology from domain to biological network levels, building better gene models, and adapting orthology approaches to the broad evolutionary and genomic diversity recognized in different forms of life and viruses.
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12. |
- Nevers, Yannis, et al.
(author)
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The Quest for Orthologs orthology benchmark service in 2022
- 2022
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 50:W1, s. W623-W632
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Journal article (peer-reviewed)abstract
- The Orthology Benchmark Service (https://orthology.benchmarkservice.org) is the gold standard for orthology inference evaluation, supported and maintained by the Quest for Orthologs consortium. It is an essential resource to compare existing and new methods of orthology inference (the bedrock for many comparative genomics and phylogenetic analysis) over a standard dataset and through common procedures. The Quest for Orthologs Consortium is dedicated to maintaining the resource up to date, through regular updates of the Reference Proteomes and increasingly accessible data through the OpenEBench platform. For this update, we have added a new benchmark based on curated orthology assertion from the Vertebrate Gene Nomenclature Committee, and provided an example meta-analysis of the public predictions present on the platform.
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13. |
- Patalano, Solenn, et al.
(author)
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Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies
- 2015
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:45, s. 13970-13975
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Journal article (peer-reviewed)abstract
- Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity.
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14. |
- Piskur, Jure, et al.
(author)
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The genome of wine yeast Dekkera bruxellensis provides a tool to explore its food-related properties.
- 2012
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In: International Journal of Food Microbiology. - : Elsevier BV. - 0168-1605. ; 157:2, s. 202-209
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Journal article (peer-reviewed)abstract
- The yeast Dekkera/Brettanomyces bruxellensis can cause enormous economic losses in wine industry due to production of phenolic off-flavor compounds. D. bruxellensis is a distant relative of baker's yeast Saccharomyces cerevisiae. Nevertheless, these two yeasts are often found in the same habitats and share several food-related traits, such as production of high ethanol levels and ability to grow without oxygen. In some food products, like lambic beer, D. bruxellensis can importantly contribute to flavor development. We determined the 13.4Mb genome sequence of the D. bruxellensis strain Y879 (CBS2499) and deduced the genetic background of several "food-relevant" properties and evolutionary history of this yeast. Surprisingly, we find that this yeast is phylogenetically distant to other food-related yeasts and most related to Pichia (Komagataella) pastoris, which is an aerobic poor ethanol producer. We further show that the D. bruxellensis genome does not contain an excess of lineage specific duplicated genes nor a horizontally transferred URA1 gene, two crucial events that promoted the evolution of the food relevant traits in the S. cerevisiae lineage. However, D. bruxellensis has several independently duplicated ADH and ADH-like genes, which are likely responsible for metabolism of alcohols, including ethanol, and also a range of aromatic compounds.
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15. |
- Richards, Stephen, et al.
(author)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Journal article (peer-reviewed)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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16. |
- Sun, Yu, 1983-
(author)
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Genome Evolution of Neurospora tetrasperma
- 2013
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Doctoral thesis (other academic/artistic)abstract
- In this thesis work, I have used a comparative genomics approach to study a fungal model organism, Neurospora tetrasperma. My specific focus has been on genomic introgression, intron evolution, chromosomal structural rearrangements and codon usage. All of the studies are based on large-scale dataset generated by next-generation sequencing technology (NGS), combined with other techniques, such as Optical Mapping. In the introgression study, we detected large-scale introgression tracts in three N. tetrasperma lineages, and the introgression showed allele-specific and chromosomal-specific pattern. In the study of introns, we found indications of mRNA mediated intron loss and non-homologous end joining (NHEJ) mediated intron gains in N. tetrasperma. We found that selection is involved in shaping intron gains and losses, and associated with intron position, intron phase and GC content. In the study of chromosomal structural rearrangements, we found a lineage specific chromosomal inversion pattern in N. tetrasperma, which indicates that inversions are unlikely to associate with the origin of the suppressed recombination and the mating system transition in N. tetrasperma. The result suggests inversions are the consequences, rather than the causes, of suppressed recombination on the mating-type chromosome of N. tetrasperma. In the final study, analyses of codon usage indicated that the region of suppressed recombination in N. tetrasperma is subjected to genomic degeneration, and selection efficiency has been much reduced in this region.
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