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Start Over Descriptor "phylogenetic profiling" Publication Type Electronic Resources
4 results on '"phylogenetic profiling"'

1. Comparative phylogenetic exploration of the human mitochondrial proteome : insights into disease and metabolism

Author

Smith, Cassandra Lauren and Robinson, Alan

Subjects
616.3, Mitochondria, Phylogenetic profiling, Mitochondrial disease, Mitochondrial carriers, Non-enzymatic acetylation, Mammalian ageing
Abstract

Mitochondria are a key organelle within human cells, with functions ranging from ATP synthesis to apoptosis. Changes in mitochondrial function are associated with many diseases, as well as 'natural' processes like ageing. Mitochondria have a unique evolutionary origin, as the result of an endosymbiotic relationship between a bacterium and an archaeal cell. Therefore, the phylogenetic history of the mitochondrial proteome is also unique within the total human proteome. A new description of the genes encoding the human mitochondrial proteome - IMPI (Integrated Mitochondrial Protein Index) 2017 - provided an opportunity for exploration of mitochondrial proteome history and the application of this knowledge to the understanding of gene function, disease and ageing. To facilitate the exploration of the mitochondrial proteome, I created a manually curated dataset of 190,097 predicted orthologues of the 1,550 IMPI 2017 human genes across 359 species, using reciprocal best hit analysis as the basis for orthologue prediction. I used this to explore gene history and the potential for phylogenetic profiling to predict the function of uncharacterised genes. This inspired the use of phylogenetic profiling within two phyla of animals, to link presence and absence of metabolic genes to the function of mitochondrial transporters. Potential transport substrates were predicted for two groups of uncharacterised mitochondrial carriers. I also used the dataset to identify features of genes associated with monogenetic disease, as well as differences between recessive and dominant disease genes. A similar orthologue identification method was used to explore the total sequenced viral proteome for potential orthologues of mitochondrial proteins. This showed that a range of mitochondrial proteins are shared with viruses, potentially facilitating the co-opting of mitochondrial function during viral infection of eukaryotic cells. I then used orthology to explore the conservation of residues linked to protein acetylation and identify a link with lifespan in warm-blooded vertebrates. In conclusion, I have used orthology to further the understanding of human mitochondrial proteome history and developed applications of this information. For example, phylogenetic features of disease genes are being used as part of a wider pipeline to predict mitochondrial disease genes. Furthermore, predicted substrates of the SLC25A14/30 mitochondrial carriers are being tested. My dataset provides further opportunities to explore the evolution and function of the mitochondrion.

Published
2019
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2. An investigation of human protein interactions using the comparative method

Author

Ur-Rehman, Saif and Barker, Daniel

Subjects
612, Phylogenetic profiling, Comparative method, Dollo parsimony, Eukaryotic phylogeny, Human protein-protein interactions, Ortholog detection, Ancestral content reconstruction, Bioinformatics, Correlated gain and loss
Abstract

There is currently a large increase in the speed of production of DNA sequence data as next generation sequencing technologies become more widespread. As such there is a need for rapid computational techniques to functionally annotate data as it is generated. One computational method for the functional annotation of protein-coding genes is via detection of interaction partners. If the putative partner has a functional annotation then this annotation can be extended to the initial protein via the established principle of “guilt by association”. This work presents a method for rapid detection of functional interaction partners for proteins through the use of the comparative method. Functional links are sought between proteins through analysis of their patterns of presence and absence amongst a set of 54 eukaryotic organisms. These links can be either direct or indirect protein interactions. These patterns are analysed in the context of a phylogenetic tree. The method used is a heuristic combination of an established accurate methodology involving comparison of models of evolution the parameters of which are estimated using maximum likelihood, with a novel technique involving the reconstruction of ancestral states using Dollo parsimony and analysis of these reconstructions through the use of logistic regression. The methodology achieves comparable specificity to the use of gene coexpression as a means to predict functional linkage between proteins. The application of this method permitted a genome-wide analysis of the human genome, which would have otherwise demanded a potentially prohibitive amount of computational resource. Proteins within the human genome were clustered into orthologous groups. 10 of these proteins, which were ubiquitous across all 54 eukaryotes, were used to reconstruct a phylogeny. An application of the heuristic predicted a set of functional protein interactions in human cells. 1,142 functional interactions were predicted. Of these predictions 1,131 were not present in current protein-protein interaction databases.

Published
2012

3. Ten Years of Collaborative Progress in the Quest for Orthologs

Author

Linard, Benjamin, Ebersberger, Ingo, McGlynn, Shawn E., Glover, Natasha, Mochizuki, Tomohiro, Patricio, Mateus, Lecompte, Odile, Nevers, Yannis, Thomas, Paul D., Gabaldon, Toni, Sonnhammer, Erik, Dessimoz, Christophe, Uchiyama, Ikuo, Linard, Benjamin, Ebersberger, Ingo, McGlynn, Shawn E., Glover, Natasha, Mochizuki, Tomohiro, Patricio, Mateus, Lecompte, Odile, Nevers, Yannis, Thomas, Paul D., Gabaldon, Toni, Sonnhammer, Erik, Dessimoz, Christophe, and Uchiyama, Ikuo

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.

Published
2021
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4. Ten years of collaborative progress in the quest for orthologs

Author

Barcelona Supercomputing Center, Linard, Benjamin, Ebersberger, Ingo, McGlynn, Shawn E, Glover, Natasha, Mochizuki, Tomohiro, Gabaldón, Toni, Barcelona Supercomputing Center, Linard, Benjamin, Ebersberger, Ingo, McGlynn, Shawn E, Glover, Natasha, Mochizuki, Tomohiro, and Gabaldón, Toni

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., We thank the National Institute for Basic Biology, the Japanese Society for Bioinformatics and the Daiko Foundation for supporting the 67th NIBB Conference/The 6th Quest for Orthologs Meeting. We wish to acknowledge the following support for attending the meetings and/or writing this manuscript: EMBO Young Investigator meeting grant (to C.D.). Service and Infrastructure grant from the Swiss Institute of Bioinformatics, Swiss National Science Foundation [183723] (to C.D.); IdEX Unistra in the framework of the Investments for the future program of the French government (to O.L. and Y.N.); NSF (Award No. 1724300), KAKENHI (Grant No. JP18H01325) (to S.E.M.); support by the research funding program Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the State of Hessen, Research Center for Translational Biodiversity Genomics (TBG) (to I.E.); funding from the Wellcome Trust (108749/Z/15/Z) and the European Molecular Biology Laboratory (to M.P.); National Human Genome Research Institute, National Institutes of Health NIH (grant no. U41HG002273), National Science Foundation NSF (award no. 1917302) (to P.D.T.); Japan Society for the Promotion of Science (16H06279 and 19F19089) (to W.I. and S.C.)., Peer Reviewed, "Article signat per 14 autors/es: Benjamin Linard, Ingo Ebersberger, Shawn E McGlynn, Natasha Glover, Tomohiro Mochizuki, Mateus Patricio, Odile Lecompte, Yannis Nevers, Paul D Thomas, Toni Gabaldón, Erik Sonnhammer, Christophe Dessimoz, Ikuo Uchiyama, QFO Consortium" "Members of the Quest for Orthologs (QFO) Consortium: Adrian Altenhoff, Aida Ouangraoua, Alex Warwick Vesztrocy, Benjamin Linard, Christophe Dessimoz, Damian Szklarczyk, Dannie Durand, David Emms, David Moi, David Thybert, Erik Sonnhammer, Evgenia Kriventseva, Haiming Tang, Hirokazu Chiba, Ikuo Uchiyama, Ingo Ebersberger, Jaime Huerta-Cepas, Jesualdo Tomas Fernandez-Breis, Judith A. Blake, Leszek Pryszcz, Maria-Jesus Martin, Marina Marcet Houben, Mateus Patricio, Matthieu Muffato, Natasha Glover, Odile Lecompte, Paul D. Thomas, Philipp Schiffer, Salvador Capella-Gutierrez, Salvatore Cosentino, Shawn E McGlynn, Shigehiro Kuraku, Sofia Forslund, Steven Kelly, Suzanna Lewis, Tamsin Jones, Tarcisio Mendes de Farias, Taro Maeda, Toni Gabaldon, Wataru Iwasaki, William Pearson, Yan Wang, Yannis Nevers, Yuichiro Hara. All members acknowledged and gave their approval to the content of this manuscript.", Postprint (published version)

Published
2021

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