Volume 53 Issue 3, March 2021

The National Cancer Institute (NCI) Genomic Data Commons (GDC) contains more than 2.9 petabytes of genomic and associated clinical data from more than 60 NCI-funded and other contributed cancer genomics research projects. The GDC consists of five applications over a common data model and a common application programming interface.

Chromatin structure, specifically sites of open or accessible chromatin, regulates transcription-factor binding, thereby determining cell-type-specific gene expression. Two new studies identify a constant requirement for SWI/SNF-complex remodeling to maintain open chromatin. In both studies, acute inhibition or degradation of the BRG1 or BRM ATPase subunits through chemical or genetic methods led to a loss of chromatin accessibility, in some cases affecting transcription-factor binding and altered gene expression.

Chromosomal inversions frequently underlie distinct phenotypic variation. A new study shows that in butterflies, inversion haplotypes accumulate deleterious mutations that prevent fixation in natural populations.

A new study builds a novel deep-learning approach to unravel the syntax of transcription-factor binding from high-resolution ChIP–nexus data. In silico simulations lead to experimental validation of complex sequence-based predictions: helical periodicity and directional cooperativity between transcription factors.

Acute degradation of the BAF subunit SMARCA4 shows rapid chromatin accessibility changes, thus suggesting that maintenance of genome accessibility requires constant ATP-dependent remodeling.

Chemical inhibition of the SWI/SNF remodeling complex shows decreased accessibility and transcription factor binding within minutes. These changes are rapidly restored on inhibitor removal suggesting that accessible chromatin is regenerated continuously.

Chromosomal inversions at the mimicry locus of Heliconius numata butterflies accumulate deleterious variants. This leads to selection against homozygosity, in opposition to positive selection for mimicry, resulting in intermediate allele frequency.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

Single-cell RNA-seq analysis of iPSC neural differentiation identifies markers that predict line-to-line differences in cell fate potential and eQTLs that are specific to different stages of differentiation and that overlap with GWAS risk variants for neurological traits.

Integrative data analysis of 1,367 human iPSC lines maps common and rare regulatory variants that colocalize with loci associated with human traits and diseases.

ECCITE-seq, which combines pooled CRISPR screens with single-cell mRNA and surface protein measurements, and the computational framework mixscape identify new regulation mechanisms of PD-L1 expression.

Pooled CRISPR perturbation screens with multimodal RNA and protein single-cell profiling readout (Perturb-CITE-seq) applied to patient-derived melanoma and tumor-infiltrating lymphocyte co-cultures identifies new tumor immune evasion mechanisms.

Human disease mutations affect protein–protein interfaces in a three-dimensional structurally resolved interaction network. Predicted oncoPPIs in cancer correlate with survival and drug sensitivity, and affect growth in vitro, supporting their relevance to disease pathogenesis.

BPNet is an interpretable deep learning tool that predicts transcription-factor binding profiles from DNA sequence at base-pair resolution, enabling the identification of motifs and the regulatory syntax underlying transcription-factor binding.

Liquid chromatin Hi-C maps the intrinsic stability of associations between loci. Lamin-associated domains are most stable, whereas interactions for speckle- and polycomb-associated loci are more dynamic.

Immediate early genes in developing sensory neurons have a unique bipartite chromatin signature: H3K27ac on promoters and enhancers, and H3K27me3 on gene bodies. Polycomb marking of gene bodies inhibits productive mRNA elongation.

Genome-wide meta-analysis, fine-mapping and integrative prioritization using expression quantitative trait loci, protein interaction networks and tissue-specific expression implicate new candidate susceptibility genes for Alzheimer’s disease.

ArchR is a software suite that enables efficient and end-to-end analysis of single-cell chromatin accessibility data (scATAC-seq).