Recent publications
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Bioinformatics.: auth.: group Dessimoz

Bioinformatics. 2021 Mar 31;btab219. doi: 10.1093/bioinformatics/btab219. Online ahead of print.

OMAmer: tree-driven and alignment-free protein assignment to subfamilies outperforms closest sequence approaches

Victor Rossier 1 2 3Alex Warwick Vesztrocy 1 2 3Marc Robinson-Rechavi 4 5Christophe Dessimoz 1 2 3 5 6Affiliations expand

Abstract

Motivation: Assigning new sequences to known protein families and subfamilies is a prerequisite for many functional, comparative and evolutionary genomics analyses. Such assignment is commonly achieved by looking for the closest sequence in a reference database, using a method such as BLAST. However, ignoring the gene phylogeny can be misleading because a query sequence does not necessarily belong to the same subfamily as its closest sequence. For example, a hemoglobin which branched out prior to the hemoglobin alpha/beta duplication could be closest to a hemoglobin alpha or beta sequence, whereas it is neither. To overcome this problem, phylogeny-driven tools have emerged but rely on gene trees, whose inference is computationally expensive.

Results: Here, we first show that in multiple animal and plant datasets, 18 to 62% of assignments by closest sequence are misassigned, typically to an over-specific subfamily. Then, we introduce OMAmer, a novel alignment-free protein subfamily assignment method, which limits over-specific subfamily assignments and is suited to phylogenomic databases with thousands of genomes. OMAmer is based on an innovative method using evolutionarily-informed k-mers for alignment-free mapping to ancestral protein subfamilies. Whilst able to reject non-homologous family-level assignments, we show that OMAmer provides better and quicker subfamily-level assignments than approaches relying on the closest sequence, whether inferred exactly by Smith-Waterman or by the fast heuristic DIAMOND.

Availability: OMAmer is available from the Python Package Index (as omamer), with the source code and a precomputed database available at https://github.com/DessimozLab/omamer.

Supplementary information: Supplementary data are available at Bioinformatics online.

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Mol Biol Evol.: auth.: group Dessimoz

Mol Biol Evol. 2021 Apr 2;msab098. doi: 10.1093/molbev/msab098. Online ahead of print.

Ten years of collaborative progress in the Quest for Orthologs

Benjamin Linard 1 2Ingo Ebersberger 3 4 5Shawn E McGlynn 6 7Natasha Glover 8 9 10Tomohiro Mochizuki 6Mateus Patricio 11Odile Lecompte 12Yannis Nevers 8 9 10QFO ConsortiumPaul D Thomas 13Toni Gabaldón 14 15 16Erik Sonnhammer 17Christophe Dessimoz 8 9 10 18 19Ikuo Uchiyama 20Affiliations expand

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 6th 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 standardisation 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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Front Physiol.: co-auth.: W.Wahli

Front Physiol. 2021 Mar 17;12:587753. doi: 10.3389/fphys.2021.587753. eCollection 2021.

Invalidation of the Transcriptional Modulator of Lipid Metabolism PPARβ/δ in T Cells Prevents Age-Related Alteration of Body Composition and Loss of Endurance Capacity

Anne-Sophie Rousseau 1Joseph Murdaca 1Gwenaëlle Le Menn 1Brigitte Sibille 1Walter Wahli 2 3 4Sébastien Le Garf 1Giulia Chinetti 5Jaap G Neels 1Isabelle Mothe-Satney 1Affiliations expand

Free PMC article

Abstract

Anti-inflammatory regulatory T cells (Tregs) are the most metabolically flexible CD4+ T cells by using both glycolysis and fatty acid oxidation (FAO) which allow them to migrate in tissues. With aging, Tregs accumulate in secondary lymphoid organs and are involved in impairment of skeletal muscle (SKM) regeneration and mass maintenance. In this study, we showed that a deletion of a FAO modulator, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), specifically in T cells (KO-T PPARβ/δ), increased the number of CD4+ T cells at day 2 following a cardiotoxin-induced SKM regeneration. Older KO-T PPARβ/δ mice maintained a Tregs prevalence in lymph nodes similar to young mice. Surprisingly, KO-T PPARβ/δ mice were protected from the effects of age on lean and fat mass and endurance capacity. Our results lead us to propose an original potential role of T cell metabolism in the effects of aging on the maintenance of body composition and endurance capacity.

Keywords: aging; immunometabolism; physical capacity; regulatory T cells; skeletal muscle.

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Genome Res.: co-auth.: S.Soyk

Genome Res. 2021 Apr 2;gr.264879.120. doi: 10.1101/gr.264879.120. Online ahead of print.

Optimized sample selection for cost-efficient long-read population sequencing

Timothy Rhyker Ranallo-Benavidez 1Zachary H Lemmon 2Sebastian Soyk 3Sergey Aganezov 4William J Salerno 5Rajiv C McCoy 6Zachary B Lippman 2Michael C Schatz 6Fritz J Sedlazeck 5

Abstract

An increasingly important scenario in population genetics is when a large cohort has been genotyped using a low-resolution approach (e.g. microarrays, exome capture, short-read WGS), from which a few individuals are selected for resequencing using a more comprehensive approach, especially long-read sequencing. The subset of individuals selected should ensure that the captured genetic diversity is fully representative and includes variants across all subpopulations. For example, human variation has historically been focused on individuals with European ancestry, but this represents a small fraction of the overall diversity. To address this goal, SVCollector identifies the optimal subset of individuals for resequencing. SVCollector analyzes a population-level VCF file from a low resolution genotyping study. It then computes a ranked list of samples that maximizes the total number of variants present from a subset of a given size. To solve this optimization problem, SVCollector implements a fast greedy heuristic and an exact algorithm using integer linear programming. We apply SVCollector on simulated data, 2504 human genomes from the 1000 Genomes Project, and 3024 genomes from the 3K Rice Genomes Project and show the rankings it computes are more representative than other naive strategies. We show that when selecting an optimal subset of 100 samples in these two cohorts, SVCollector identifies individuals from every subpopulation while naive methods yield an unbalanced selection. Finally, we show the number of variants present in cohorts of different sizes selected using this approach follows a power-law distribution that is naturally related to the population genetic concept of the allele frequency spectrum, allowing us to estimate the diversity present with increasing numbers of samples.

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“L’Expérience doctorale, État des lieux et propositions de structuration”, livre PDF à télécharger gratuitement

(PDF-book on the doctoral experience only available in French)

«Un doctorat c’est une longue période de recherche individuelle, sous la houlette plus ou moins distante/bienveillante/ombrageuse… d’un·e professeur·e établi·e, dont l’horizon est un gros livre bien épais, fierté de toute une vie et que personne ne lit»…

Si vous y croyez, ou si vous croyez tout autre chose, d’ailleurs, mais que le doctorat en tant que formation et de jalon dans une vie intellectuelle et professionnelle vous intéresse, lisez de toute urgence «L’Expérience doctorale. État des lieux et propositions de structuration»!

Cet ouvrage de synthèse et de proposition publié l’an dernier par la HES-SO Haute école spécialisée est le fruit des compétences et des réflexions de 4 excellent·e·s spécialistes: Denis Berthiaume, Mélanie Bosson, Verity Elston et Isabelle Skakni.
À la CUSO, nous avons la chance et le plaisir de travailler tour à tour avec les 4 personnes, et d’apprécier leur savoir et leur acuité.

À télécharger librement sur https://devpro.hes-so.ch/…/Experience-doctorale-DevPro-juin…

L’avant-propos est signé du secrétaire général de la CUSO Denis Billotte.
#doctorat #PhD #doctoraleducation

Un exemplaire imprimé est à disposition dans le bureau de Corinne Dentan (GEN 4006)

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Congratulations to B.Thorens on his Roger Assan prize !

Le Prix Roger Assan, doté d’une bourse de 10’000 €, récompense un·e clinicien·ne ou chercheur·euse de réputation internationale ayant effectué l’essentiel de sa carrière dans des pays francophones, et dont les travaux ont amené à des avancées majeures et ouvert de nouvelles voies dans la compréhension ou le traitement du diabète et des maladies métaboliques.

Lire l’article complet: https://news.unil.ch/display/1615213027799
Informations sur la société Francophone du Diabète: https://www.sfdiabete.org/medical/la-recherche/appels-candidature/prix-roger-assan#videos