New metrics for comparative genomics

Galperin, Michael Y.; Kolker, Eugene

doi:10.1016/j.copbio.2006.08.007

Cited by 32 publications

(32 citation statements)

References 61 publications

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“…A functional analysis of the regulated genes further revealed that, whereas the regulated MC58-specific genes are evenly distributed over all COG functional classes (P ϭ 0.77, 2 test) (22,76), the regulated core genes in the corresponding three data sets are enriched for genes coding for metabolic functions ( Fig. 5; also see Table S4 in the supplemental material).…”

Section: Vol 192 2010mentioning

confidence: 99%

“…Therefore, we provide here the first high-quality draft sequence of a genome from the ST-136 serogroup B carriage isolate ␣710 (13) and compared it to the genome of strain MC58 (77) with respect to the predicted functions and subcellular localizations of the encoded proteins (22). We further compared the transcriptomes of both strains upon adhesion to human nasopharyngeal cell lines to comprehensively capture genetic differences between these two serogroup B meningococcal strains on a genome-wide scale.…”

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confidence: 99%

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Comparative Genome Biology of a Serogroup B Carriage and Disease Strain Supports a Polygenic Nature of Meningococcal Virulence

et al. 2010

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Neisseria meningitidis serogroup B strains are responsible for most meningococcal cases in the industrialized countries, and strains belonging to the clonal complex ST-41/44 are among the most prevalent serogroup B strains in carriage and disease. Here, we report the first genome and transcriptome comparison of a serogroup B carriage strain from the clonal complex ST-41/44 to the serogroup B disease strain MC58 from the clonal complex ST-32. Both genomes are highly colinear, with only three major genome rearrangements that are associated with the integration of mobile genetic elements. They further differ in about 10% of their gene content, with the highest variability in gene presence as well as gene sequence found for proteins involved in host cell interactions, including Opc, NadA, TonB-dependent receptors, RTX toxin, and two-partner secretion system proteins. Whereas housekeeping genes coding for metabolic functions were highly conserved, there were considerable differences in their expression pattern upon adhesion to human nasopharyngeal cells between both strains, including differences in energy metabolism and stress response. In line with these genomic and transcriptomic differences, both strains also showed marked differences in their in vitro infectivity and in serum resistance. Taken together, these data support the concept of a polygenic nature of meningococcal virulence comprising differences in the repertoire of adhesins as well as in the regulation of metabolic genes and suggest a prominent role for immune selection and genetic drift in shaping the meningococcal genome.

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Section: Vol 192 2010mentioning

confidence: 99%

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confidence: 99%

Comparative Genome Biology of a Serogroup B Carriage and Disease Strain Supports a Polygenic Nature of Meningococcal Virulence

et al. 2010

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“…The currency for reasoning by comparative genomics to infer molecular functions and biological processes consists mostly of highly derived data , often very far removed from the lists of which specific protein sequences have had which functions proven in the lab [5]. We use HMM-based classifications of proteins into families to tell what enzymes are present in a microbe, then combinations of these assignments to assert that an enzymatic pathway or other subsystem is complete, or else completely absent, for any given genome.…”

Section: Derived Datamentioning

confidence: 99%

Using comparative genomics to drive new discoveries in microbiology

Haft

2015

Current Opinion in Microbiology

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Bioinformatics looks to many microbiologists like a service industry. In this view, annotation starts with what is known from experiments in the lab, makes reasonable inferences of which genes match other genes in function, builds databases to make all that we know accessible, but creates nothing truly new. Experiments lead, then biocuration and computational biology follow. But the astounding success of genome sequencing is changing the annotation paradigm. Every genome sequenced is an intercepted coded message from the microbial world, and as all cryptographers know, it is easier to decode a thousand messages than a single message. Some biology is best discovered not by phenomenology, but by decoding genome content, forming hypotheses, and doing the first few rounds of validation computationally. Through such reasoning, a role and function may be assigned to a protein with no sequence similarity to any protein yet studied. Experimentation can follow after the discovery to cement and to extend the findings. Unfortunately, this approach remains so unfamiliar to most bench scientists that lab work and comparative genomics typically segregate to different teams working on unconnected projects. This review will discuss several themes in comparative genomics as a discovery method, including highly derived data, use of patterns of design to reason by analogy, and in silico testing of computationally generated hypotheses.

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“…In contrast to sequence, encoded in a non-ambiguous manner by a chain of amino-acid letters, the function of an enzyme is a fuzzy notion, especially for enzymes presenting a broad specificity such as CYPs. Building a phylogenetic tree is made simple by a metric of standard distances that link any sequence alignment to a score of sequence similarity [55]. Enzyme function sharply contrasts with this situation since it requires a multidimensional definition more difficult to express.…”

Section: Data Pre-processing (Normalization)mentioning

confidence: 99%

Differences in Functional Clustering of Endogenous and Exogenous Substrates Between Members of the CYP1A Subfamily

Urban¹,

Truan²,

Pompon³

2009

Open Drug Metab J

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Abstract:The ability of four mammalian cytochromes P450 (CYP) of the CYP1A subfamily, human and mouse CYP1A1s and human and rabbit CYP1A2s, to metabolize a series of steroids and related compounds was investigated using high throughput approaches. Oxidation rates and metabolite patterns for 16 steroid substrates and for 20 polycyclic aromatic hydrocarbon (PAH) substrates were determined in standardized automated conditions. Multivariate statistics of normalized activity data sets was used to sort out significant information and to compare functional signatures of assayed enzymes. Interestingly, for steroid substrates, rabbit CYP1A2 unambiguously aggregates with human and mouse CYP1A1s and appears functionally divergent from human CYP1A2. In contrast, the functional classification was found consistent with the sequence classification when exogenous PAH substrates were tested. The observed features rely on a large set of substrates, all presenting a similar chemical scaffold but decorated with different substituents similar to chemical series used in drug development. Differential functional clusters are thus evidenced for endogenous and exogenous substrates with CYP1A enzymes. A few residues on rabbit CYP1A2 that may account for its unusual 1A1-like specificity toward steroids have been identified both within the active site and at the protein surface. These specific residues thus seem to play a controlling role for global substrate class discrimination, potentially by involving substrate bulkiness and shape sensing.

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New metrics for comparative genomics

Cited by 32 publications

References 61 publications

Comparative Genome Biology of a Serogroup B Carriage and Disease Strain Supports a Polygenic Nature of Meningococcal Virulence

Comparative Genome Biology of a Serogroup B Carriage and Disease Strain Supports a Polygenic Nature of Meningococcal Virulence

Using comparative genomics to drive new discoveries in microbiology

Differences in Functional Clustering of Endogenous and Exogenous Substrates Between Members of the CYP1A Subfamily

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