Dataset Information

ADME SARfari: comparative genomics of drug metabolizing systems.

ABSTRACT:

Motivation

ADME SARfari is a freely available web resource that enables comparative analyses of drug-disposition genes. It does so by integrating a number of publicly available data sources, which have subsequently been used to build data mining services, predictive tools and visualizations for drug metabolism researchers. The data include the interactions of small molecules with ADME (absorption, distribution, metabolism and excretion) proteins responsible for the metabolism and transport of molecules; available pharmacokinetic (PK) data; protein sequences of ADME-related molecular targets for pre-clinical model species and human; alignments of the orthologues including information on known SNPs (Single Nucleotide Polymorphism) and information on the tissue distribution of these proteins. In addition, in silico models have been developed, which enable users to predict which ADME relevant protein targets a novel compound is likely to interact with.

SUBMITTER: Davies M

PROVIDER: S-EPMC4426839 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ADME SARfari: comparative genomics of drug metabolizing systems.

Davies Mark M Dedman Nathan N Hersey Anne A Papadatos George G Hall Matthew D MD Cucurull-Sanchez Lourdes L Jeffrey Phil P Hasan Samiul S Eddershaw Peter J PJ Overington John P JP

Bioinformatics (Oxford, England) 20150108 10

<h4>Motivation</h4>ADME SARfari is a freely available web resource that enables comparative analyses of drug-disposition genes. It does so by integrating a number of publicly available data sources, which have subsequently been used to build data mining services, predictive tools and visualizations for drug metabolism researchers. The data include the interactions of small molecules with ADME (absorption, distribution, metabolism and excretion) proteins responsible for the metabolism and transpo ...[more]

PMID: 25964657

Similar Datasets

Project description:Chemosensory systems (CSS) are among the most complex organizations of proteins functioning cooperatively to regulate bacterial motility and other cellular activities. These systems have been studied extensively in bacteria, and usually, they are present as a single system. Eight CSS, the highest number in bacteria, have been reported in Myxococcus xanthus DK1622 and are involved in coordinating diverse functions. Here, we have explored and compared the CSS in all available genomes of order Myxococcales. Myxococcales members contain 97 to 476 two-component system (TCS) proteins, which assist the bacteria in surviving and adapting to varying environmental conditions. The number of myxobacterial CSS ranges between 1 and 12, with the largest number in family Cystobacteraceae and the smallest in Nannocystaceae CheA protein was used as a phylogenetic marker to infer evolutionary relatedness between different CSS, and six novel CSS ("extra CSS" [ECSS]) were thus identified in the myxobacteria besides the previously reported Che1 to Che8 systems from M. xanthus Che1 to Che8 systems are monophyletic to deltaproteobacteria, whereas the newly identified ECSS form separate clades with different bacterial classes. The comparative modular organization was concordant with the phylogeny. Four clusters lacking CheA proteins were also identified via CheB-based phylogenetic analysis and were categorized as accessory CSS (ACSS). In Archangium, an orphan CSS was identified, in which both CheA and CheB were absent. The novel, accessory, and orphan multimodular CSS identified here suggest the emergence of myxobacterial CSS and could assist in further characterizing their roles.IMPORTANCE This study is focused on chemosensory systems (CSS), which help the bacterium in directing its movement toward or away from chemical gradients. CSS are present as a single system in most of the bacteria except in some groups, including Myxococcus xanthus, which has 8 CSS, the highest number reported to date. This is the first comprehensive study carrying out a comparative analysis of the 22 available myxobacterial genomes, which suggests the evolutionary diversity of these systems. We are interested in understanding the distribution of CSS within all known myxobacteria and their probable evolution.

Project description:BackgroundTuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador.ResultsGenomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected.ConclusionThis work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies.

Dataset Information

ADME SARfari: comparative genomics of drug metabolizing systems.

Motivation

Publications

ADME SARfari: comparative genomics of drug metabolizing systems.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets