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2.
PLoS Comput Biol ; 16(3): e1007732, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32191703

RESUMO

The use of comparative genomics for functional, evolutionary, and epidemiological studies requires methods to classify gene families in terms of occurrence in a given species. These methods usually lack multivariate statistical models to infer the partitions and the optimal number of classes and don't account for genome organization. We introduce a graph structure to model pangenomes in which nodes represent gene families and edges represent genomic neighborhood. Our method, named PPanGGOLiN, partitions nodes using an Expectation-Maximization algorithm based on multivariate Bernoulli Mixture Model coupled with a Markov Random Field. This approach takes into account the topology of the graph and the presence/absence of genes in pangenomes to classify gene families into persistent, cloud, and one or several shell partitions. By analyzing the partitioned pangenome graphs of isolate genomes from 439 species and metagenome-assembled genomes from 78 species, we demonstrate that our method is effective in estimating the persistent genome. Interestingly, it shows that the shell genome is a key element to understand genome dynamics, presumably because it reflects how genes present at intermediate frequencies drive adaptation of species, and its proportion in genomes is independent of genome size. The graph-based approach proposed by PPanGGOLiN is useful to depict the overall genomic diversity of thousands of strains in a compact structure and provides an effective basis for very large scale comparative genomics. The software is freely available at https://github.com/labgem/PPanGGOLiN.


Assuntos
Genoma Bacteriano/genética , Genômica/métodos , Software , Algoritmos , Bactérias/classificação , Bactérias/genética , Análise Multivariada
3.
Brief Bioinform ; 20(4): 1071-1084, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28968784

RESUMO

The overwhelming list of new bacterial genomes becoming available on a daily basis makes accurate genome annotation an essential step that ultimately determines the relevance of thousands of genomes stored in public databanks. The MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Starting from the results of our syntactic, functional and relational annotation pipelines, MicroScope provides an integrated environment for the expert annotation and comparative analysis of prokaryotic genomes. It combines tools and graphical interfaces to analyze genomes and to perform the manual curation of gene function in a comparative genomics and metabolic context. In this article, we describe the free-of-charge MicroScope services for the annotation and analysis of microbial (meta)genomes, transcriptomic and re-sequencing data. Then, the functionalities of the platform are presented in a way providing practical guidance and help to the nonspecialists in bioinformatics. Newly integrated analysis tools (i.e. prediction of virulence and resistance genes in bacterial genomes) and original method recently developed (the pan-genome graph representation) are also described. Integrated environments such as MicroScope clearly contribute, through the user community, to help maintaining accurate resources.


Assuntos
Genoma Microbiano , Genômica/métodos , Anotação de Sequência Molecular/métodos , Software , Biologia Computacional , Gráficos por Computador , Sistemas de Gerenciamento de Base de Dados , Bases de Dados de Compostos Químicos , Genômica/estatística & dados numéricos , Internet , Redes e Vias Metabólicas/genética , Fenômenos Microbiológicos , Anotação de Sequência Molecular/estatística & dados numéricos , Interface Usuário-Computador
4.
Nucleic Acids Res ; 45(D1): D517-D528, 2017 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-27899624

RESUMO

The annotation of genomes from NGS platforms needs to be automated and fully integrated. However, maintaining consistency and accuracy in genome annotation is a challenging problem because millions of protein database entries are not assigned reliable functions. This shortcoming limits the knowledge that can be extracted from genomes and metabolic models. Launched in 2005, the MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Effective comparative analysis requires a consistent and complete view of biological data, and therefore, support for reviewing the quality of functional annotation is critical. MicroScope allows users to analyze microbial (meta)genomes together with post-genomic experiment results if any (i.e. transcriptomics, re-sequencing of evolved strains, mutant collections, phenotype data). It combines tools and graphical interfaces to analyze genomes and to perform the expert curation of gene functions in a comparative context. Starting with a short overview of the MicroScope system, this paper focuses on some major improvements of the Web interface, mainly for the submission of genomic data and on original tools and pipelines that have been developed and integrated in the platform: computation of pan-genomes and prediction of biosynthetic gene clusters. Today the resource contains data for more than 6000 microbial genomes, and among the 2700 personal accounts (65% of which are now from foreign countries), 14% of the users are performing expert annotations, on at least a weekly basis, contributing to improve the quality of microbial genome annotations.


Assuntos
Bases de Dados Genéticas , Metagenoma , Metagenômica/métodos , Microbiota/genética , Biologia Computacional/métodos , Evolução Molecular , Metaboloma , Metabolômica/métodos , Família Multigênica , Polimorfismo de Nucleotídeo Único , Software
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