4 research outputs found
Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking
The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data
Identification of Clinically Used Drugs That Activate Pregnane X ReceptorsS⃞
The pregnane X receptor (PXR) binds xenobiotics and regulates the expression of
several drug-metabolizing enzymes and transporters. Human PXR (hPXR) activation and
CYP3A4 induction can be involved in drug-drug interactions, resulting in reduced
efficacy or increased toxicity. However, there are known species-specific differences
with regard to PXR activation that should be taken into account when animal PXR data
are extrapolated to humans. We profiled 2816 clinically used drugs from the National
Institutes of Health Chemical Genomics Center Pharmaceutical Collection for their
ability to activate hPXR and rat PXR (rPXR) at the cellular level, induce human
CYP3A4 at the cellular level, and bind human PXR at the protein level. From 6 to 11%
of drugs were identified as active across the four assays, which included
assay-specific and pan-active compounds. The lowest concordance was observed between
the hPXR and rPXR assays, and many compounds active in both assays nonetheless
demonstrated significant potency differences between species. Analysis based on
clustering potency values demonstrated the greatest activity correlation between the
hPXR activation and CYP3A4 induction assays. Structure-activity relationship analysis
identified chemical scaffolds that were pan-active (e.g., dihydropyridine calcium
channel blockers) and others that were uniquely active in individual assays (e.g.,
steroids and fatty acids). These results provide important information on PXR
activation by clinically used drugs, highlight the species specificity of PXR
activation by xenobiotics, and provide a means of prioritizing compounds for
follow-up studies and optimization efforts
Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking
The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data