Topological orbit equivalence of locally compact Cantor minimal systems

Minimal homeomorphisms on the locally compact Cantor set are investigated. We prove that scaled dimension groups modulo infinitesimal subgroups determine topological orbit equivalence classes of locally compact Cantor minimal systems.･･

Additional file 3: Table S3. of Application of dynamic topic models to toxicogenomics data

Functional analysis results for each topic at 4 time points: Fisher’s exact test with a p value cut-off of 0.05 was used in KEGG and GO. (XLSX 82 kb

Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells

The new strategy for chemical toxicity testing and modeling is to use in vitro human cell-based assays in conjunction with quantitative high-throughput screening (qHTS) technology, to identify molecular mechanisms and predict in vivo responses. Stem cells are more physiologically relevant than immortalized cell lines because of their unique proliferation and differentiation potentials. We established a robust two stem cells-two lineages assay system, encompassing human mesenchymal stem cells (hMSCs) along osteogenesis and human induced pluripotent stem cells (hiPSCs) along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280 and identified 38 preliminary hits for hMSCs. This was followed by validation of a selected number of hits and determination of their IC₅₀ values and mechanistic studies of idarubicin and cantharidin treatments using proteomics and bioinformatics. In general, hiPSCs were more sensitive than hMSCs to chemicals, and differentiated progenies were less sensitive than their progenitors. We showed that chemical toxicity depends on both stem cell types and their differentiation stages. Proteomics identified and quantified over 3000 proteins for both stem cells. Bioinformatics identified apoptosis and G2/M as the top pathways conferring idarubicin toxicity. Our Omics-based assays of stem cells provide mechanistic insights into chemical toxicity and may help prioritize chemicals for in-depth toxicological evaluations

Distribution of the number of enriched gene targets for each cluster.

Distribution of the number of enriched gene targets for each cluster.</p

A contingency table for gene target enrichment analysis.

A contingency table for gene target enrichment analysis.</p

Associations between ERBB2 and Posaconazole.

The details can be found at https://arax.ncats.io/?r=66179.</p

Overview of the drug repurposing framework.

Drug repurposing is a strategy for identifying new uses of approved or investigational drugs that are outside the scope of the original medical indication. Even though many repurposed drugs have been found serendipitously in the past, the increasing availability of large volumes of biomedical data has enabled more systemic, data-driven approaches for drug candidate identification. At National Center of Advancing Translational Sciences (NCATS), we invent new methods to generate new data and information publicly available to spur innovation and scientific discovery. In this study, we aimed to explore and demonstrate biomedical data generated and collected via two NCATS research programs, the Toxicology in the 21st Century program (Tox21) and the Biomedical Data Translator (Translator) for the application of drug repurposing. These two programs provide complementary types of biomedical data from uncovering underlying biological mechanisms with bioassay screening data from Tox21 for chemical clustering, to enrich clustered chemicals with scientific evidence mined from the Translator towards drug repurposing. 129 chemical clusters have been generated and three of them have been further investigated for drug repurposing candidate identification, which is detailed as case studies.</div

Gene-compound association discovery for the GPCR enriched cluster #1.

Gene-compound association discovery for the GPCR enriched cluster #1.</p

Overlap in genes and compounds between Pharos and the BDRH.

a) more gene targets were found in the BDRH than via Pharos; b) Pharos had more compounds than BDRH.</p

S2 Data -

Drug repurposing is a strategy for identifying new uses of approved or investigational drugs that are outside the scope of the original medical indication. Even though many repurposed drugs have been found serendipitously in the past, the increasing availability of large volumes of biomedical data has enabled more systemic, data-driven approaches for drug candidate identification. At National Center of Advancing Translational Sciences (NCATS), we invent new methods to generate new data and information publicly available to spur innovation and scientific discovery. In this study, we aimed to explore and demonstrate biomedical data generated and collected via two NCATS research programs, the Toxicology in the 21st Century program (Tox21) and the Biomedical Data Translator (Translator) for the application of drug repurposing. These two programs provide complementary types of biomedical data from uncovering underlying biological mechanisms with bioassay screening data from Tox21 for chemical clustering, to enrich clustered chemicals with scientific evidence mined from the Translator towards drug repurposing. 129 chemical clusters have been generated and three of them have been further investigated for drug repurposing candidate identification, which is detailed as case studies.</div