15 research outputs found
ProteomeScout: A repository and analysis resource for post-translational modifications and proteins
ProteomeScout (https://proteomescout.wustl.edu) is a resource for the study of proteins and their post-translational modifications (PTMs) consisting of a database of PTMs, a repository for experimental data, an analysis suite for PTM experiments, and a tool for visualizing the relationships between complex protein annotations. The PTM database is a compendium of public PTM data, coupled with user-uploaded experimental data. ProteomeScout provides analysis tools for experimental datasets, including summary views and subset selection, which can identify relationships within subsets of data by testing for statistically significant enrichment of protein annotations. Protein annotations are incorporated in the ProteomeScout database from external resources and include terms such as Gene Ontology annotations, domains, secondary structure and non-synonymous polymorphisms. These annotations are available in the database download, in the analysis tools and in the protein viewer. The protein viewer allows for the simultaneous visualization of annotations in an interactive web graphic, which can be exported in Scalable Vector Graphics (SVG) format. Finally, quantitative data measurements associated with public experiments are also easily viewable within protein records, allowing researchers to see how PTMs change across different contexts. ProteomeScout should prove useful for protein researchers and should benefit the proteomics community by providing a stable repository for PTM experiments
Modeling Small-Molecule Reactivity Identifies Promiscuous Bioactive Compounds
Scientists rely on
high-throughput screening tools to identify
promising small-molecule compounds for the development of biochemical
probes and drugs. This study focuses on the identification of promiscuous
bioactive compounds, which are compounds that appear active in many
high-throughput screening experiments against diverse targets but
are often false-positives which may not be easily developed into successful
probes. These compounds can exhibit bioactivity due to nonspecific,
intractable mechanisms of action and/or by interference with specific
assay technology readouts. Such “frequent hitters” are
now commonly identified using substructure filters, including pan
assay interference compounds (PAINS). Herein, we show that mechanistic
modeling of small-molecule reactivity using deep learning can improve
upon PAINS filters when modeling promiscuous bioactivity in PubChem
assays. Without training on high-throughput screening data, a deep
learning model of small-molecule reactivity achieves a sensitivity
and specificity of 18.5% and 95.5%, respectively, in identifying promiscuous
bioactive compounds. This performance is similar to PAINS filters,
which achieve a sensitivity of 20.3% at the same specificity. Importantly,
such reactivity modeling is complementary to PAINS filters. When PAINS
filters and reactivity models are combined, the resulting model outperforms
either method alone, achieving a sensitivity of 24% at the same specificity.
However, as a probabilistic model, the sensitivity and specificity
of the deep learning model can be tuned by adjusting the threshold.
Moreover, for a subset of PAINS filters, this reactivity model can
help discriminate between promiscuous and nonpromiscuous bioactive
compounds even among compounds matching those filters. Critically,
the reactivity model provides mechanistic hypotheses for assay interference
by predicting the precise atoms involved in compound reactivity. Overall,
our analysis suggests that deep learning approaches to modeling promiscuous
compound bioactivity may provide a complementary approach to current
methods for identifying promiscuous compounds
CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer
CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine
Between political rhetoric and realpolitik calculations: Western diplomacy and the Baltic independence struggle in the Cold War endgame
Fifteen years after the Baltic SSRs' independence declarations, this article sheds new light on the Estonian, Latvian and Lithuanian struggle to regain statehood in the context of international relations between 1988 and 1991. Based on declassified archival sources from Western and Eastern archives, memoirs and official histories, it reveals the nature of 'Western' Baltic policies and analyses how (far) they impacted on the Soviet Union's demise. Second, the role universal normative values played in Western, Soviet and Baltic politics will be discussed in historical perspective; with the article concluding by offering some reflections on the general relationship between political rhetoric and foreign policy