Updating and curating metabolic pathways of TB

Jocelyne Lew
Churchill Livingstone, 2013
Article

Résumé

The sequencing of complete genomes has accelerated biomedical research by providing information about the overall coding capacity of bacterial chromosomes. The original TB annotation resulted in putative functional assignment of similar to 60% of the genes to specific metabolic functions, however, the other 40% of the encoded ORFs where annotated as conserved hypothetical proteins, hypothetical proteins or encoding proteins of unknown function. The TB research community is now at the beginning of the next phases of post-genomics; namely reannotation and functional characterization by targeted experimentation. Arguably, this is the most significant time for basic microbiology in recent history. To foster basic TB research, the Tuberculosis Community Annotation Project (TBCAP) jamboree exercise began the reannotation effort by providing additional information for previous annotations, and refining and substantiating the functional assignment of ORFs and genes within metabolic pathways. The overall goal of the TBCAP 2012 exercise was to gather and compile various data types and use this information with oversight from the scientific community to provide additional information to support the functional annotations of encoding genes. Another objective of this effort was to standardize the publicly accessible Mycobacterium tuberculosis reference sequence and its annotation. The greatest benefit of functional annotation information of genome sequence is that it fuels TB research for drug discovery, diagnostics, vaccine development and epidemiology. (C) 2012 Elsevier Ltd. All rights reserved.

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https://infoscience.epfl.ch/record/185506?ln=fr

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Jocelyne Lew
Churchill Livingstone, 2013
Article

Résumé

Official source

https://infoscience.epfl.ch/record/185506?ln=fr

À propos de ce résultat

Concepts associés (16)

Concepts associés

Chargement

Publications associées (16)

Publications associées

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New Genome Similarity Measures based on Conserved Gene Adjacencies

Shachi Shailesh Deshpande, Bernard Moret

Many important questions in molecular biology, evolution, and biomedicine can be addressed by comparative genomic approaches. One of the basic tasks when comparing genomes is the definition of measures of similarity (or dissimilarity) between two genomes, for example, to elucidate the phylogenetic relationships between species. The power of different genome comparison methods varies with the underlying formal model of a genome. The simplest models impose the strong restriction that each genome under study must contain the same genes, each in exactly one copy. More realistic models allow several copies of a gene in a genome. One speaks of gene families, and comparative genomic methods that allow this kind of input are called gene family-based. The most powerfulbut also most complexmodels avoid this preprocessing of the input data and instead integrate the family assignment within the comparative analysis. Such methods are called gene family-free. In this article, we study an intermediate approach between family-based and family-free genomic similarity measures. Introducing this simpler model, called gene connections, we focus on the combinatorial aspects of gene family-free genome comparison. While in most cases, the computational costs to the general family-free case are the same, we also find an instance where the gene connections model has lower complexity. Within the gene connections model, we define three variants of genomic similarity measures that have different expression powers. We give polynomial-time algorithms for two of them, while we show NP-hardness for the third, most powerful one. We also generalize the measures and algorithms to make them more robust against recent local disruptions in gene order. Our theoretical findings are supported by experimental results, proving the applicability and performance of our newly defined similarity measures.

Mary Ann Liebert2017

Chargement

Single nucleotide polymorphisms (SNPs) are likely to contribute to the study of complex genetic diseases. The genomic sequence of human chromosome 21q was recently completed with 225 annotated genes, thus permitting efficient identification and precise mapping of potential cSNPs by bioinformatics approaches. Here we present a human chromosome 21 (HC21) cSNP database and the first chromosome-specific cSNP map. Potential cSNPs were generated using three approaches: (1) Alignment of the complete HC21 genomic sequence to cognate ESTs and mRNAs. Candidate cSNPs were automatically extracted using a novel program for context-dependent SNP identification that efficiently discriminates between true variation, poor quality sequencing, and paralogous gene alignments. (2) Multiple alignment of all known HC21 genes to all other human database entries. (3) Gene-targeted cSNP discovery. To date we have identified 377 cSNPs averaging ~1 SNP per 1.5 kb of transcribed sequence, covering 65% of known genes in the chromosome. Validation of our bioinformatics approach was demonstrated by a confirmation rate of 78% for the predicted cSNPs, and in total 32% of the cSNPs in our database have been confirmed. The database is publicly available at http://csnp.unige.ch or http://csnp.isb-sib.ch. These SNPs provide a tool to study the contribution of HC21 loci to complex diseases such as bipolar affective disorder and allele-specific contributions to Down syndrome phenotypes.

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DCJ median problems on linear multichromosomal genomes: Graph representation and fast exact solutions

Wei Xu

Given a set of genomes g and a distance measure d, the genome rearrangement median problem asks for another genome q that minimizes Sigma n is an element of g(d(q,g)). This problem lies at the heart of phylogenetic reconstruction from rearrangement data. where Solutions to the median problems are iteratively used to update genome assignments to internal nodes for a given tree. The median problem for reversal distance and DCJ distance is known to be NP-hard. regardless of whether genomes contain circular chromosomes or linear chromosomes and of whether extra circular chromosomes is allowed in the median genomes. In this paper, we study the relaxed DCJ median problem on linear multichromosomal genomes where the median genomes may contain extra circular chromosomes. extend our prior results on circular genomes-which allowed us to compute exact medians for genomes of up to 1,000 genes within a few minutes. First we model the DCJ median problem on linear multichromosomal genomes by a cupped multiple break-point graph, a model that avoids another computationally difficult problem-a multi-way capping problem for linear genomes, then establish its corresponding decomposition theory, and finally show its results on genomes with up to several thousand genes.

Springer2009

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New Genome Similarity Measures based on Conserved Gene Adjacencies

Shachi Shailesh Deshpande, Bernard Moret

Mary Ann Liebert2017