Systems & Computational Biology
KAP1 is an antiparallel dimer with a functional asymmetryThis study reveals the architecture of human KAP1 by integrating molecular modeling with small-angle X-ray scattering and single-molecule experiments. KAP1 dimers feature a structural asymmetry at the C-terminal domains that has functional implications for recruitment of HP1.
Targeted variant detection using unaligned RNA-Seq readsThis study introduces km, an approach leveraging k-mer decomposition to identify targeted mutations. It can detect single-base mutations, insertions and deletions, as well as fusions. An analysis of over 10,000 RNA-seq samples shows fast mutation detection via km.
Dietary restriction induces posttranscriptional regulation of longevity genesBy modulating posttranscriptional processes, including RNA editing, miRNA biogenesis, and intron retention, dietary restriction enacts some of its pro-longevity benefits in Caenorhabditis elegans through posttranscriptional regulation of gene expression.
Cellular response upon proliferation in the presence of an active mitotic checkpointCells that replicate with an active mitotic checkpoint remain capable to mount multiple times an efficient arrest, are bigger than unperturbed cells, rely more heavily on Cdh1, and have an altered protein expression profile.
Competition in the chaperone-client network subordinates cell-cycle entry to growth and stressGrowth and cell-cycle entry compete for multifunctional chaperones subjugating the critical size and proliferation to the growth potential of the cell.
A network of human functional gene interactions from knockout fitness screens in cancer cellsThe function of human genes can be strongly inferred from their knockout fitness profiles across hundreds of CRISPR screens, illuminating the modular organization of the cell.
The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical mannerPI3K and p38 act in a hierarchical manner to enhance mTORC1 activity and stress granule formation; although PI3K is the main driver, the impact of p38 gets apparent as PI3K activity declines.
A junction coverage compatibility score to quantify the reliability of transcript abundance estimates and annotation catalogsComparison of observed exon–exon junction counts to those predicted from estimated transcript abundances can identify genes with misannotated or misquantified transcripts.
An integrative machine learning approach for prediction of toxicity-related drug safetyThis method allows the prediction of toxicity-related drug clinical trial failures, withdrawals from the market, and idiosyncratic toxicity risk by combining biological network analysis with machine learning.
Interaction modulation through arrays of clustered methyl-arginine protein modificationsExtensively modifiable arrays of clustered arginines in a large set of human proteins function as regulatory protein interaction platforms. Quantitative immunoprecipitation assays defined two distinct cumulative binding mechanisms operating across an array of 18 methyl-arginine motifs in SYNCRIP.