Biomedicine Daily · Monday, 28 September 2026
CBA FRONTIER INSIGHTS
Multi-omic atlas maps gene regulation across 21 human tissues
A single-nucleus multi-omic atlas covering 21 adult human tissues from four donors profiles 459,856 nuclei, including 160,688 with paired transcriptome and chromatin accessibility data. The resource resolves 313 cell subclusters and identifies 1,085,062 candidate cis-regulatory elements, 161,270 of them novel, along with 871,177 links between candidate regulatory elements and genes. Sequence-to-function models trained on the data flag 18,133 high-effect fine-mapped variants, giving researchers a framework for interpreting non-coding disease risk. Elsewhere on the day: a CRISPR interference screen shows glioblastoma cells are largely insensitive to repression of RNA polymerase III genes, and a pediatric pan-cancer classifier, FRANK, reached 98.3% accuracy distinguishing 181 childhood tumor and normal tissue types across 16,398 validation samples.
Research papers
A single-nucleus multi-omic atlas of gene regulation across 21 adult human tissues
A single-nucleus multi-omic atlas maps gene regulation across 21 adult human tissues from four donors, profiling 459,856 nuclei including 160,688 with paired transcriptome and chromatin accessibility. It resolves 313 subclusters and identifies 1,085,062 candidate cis-regulatory elements, 161,270 of them novel, plus 871,177 cCRE-gene links. Trained sequence-to-function models flag 18,133 high-effect fine-mapped variants, giving a framework for interpreting non-coding risk.
Targeted CRISPRi screening reveals unexpected resilience across the RNA polymerase III transcriptome
An inducible CRISPR interference platform with a custom sgRNA library enabled gene-specific repression of RNA polymerase III-transcribed genes and Pol III machinery. Genome-wide screens in diploid fibroblasts and HEK293T cells uncovered several Pol III dependencies, with multiple initiator methionine tRNA genes among the strongest fitness dependencies. Glioblastoma models, however, remained largely insensitive to repression of both individual Pol III genes and core Pol III components despite efficient target knockdown, challenging the assumption that cancer cells uniformly depend on elevated Pol III activity.
Integrative Nanopore and Illumina sequencing reveals age-associated tRNA modification and CCA-tail dynamics in yeast
Nanopore direct RNA sequencing (RNA004 chemistry) with Illumina validation profiles the Saccharomyces cerevisiae tRNAome during replicative aging at single-molecule resolution. Overall tRNA abundance remains largely stable, but aging brings terminal A cleavage at the 3' CCA tail of mature tRNAs, targeted T-loop and anticodon modification changes, and single-molecule evidence of modification co-occurrence. The work adds a benchmarked resource for studying tRNA regulation, translation fidelity, and longevity.
Methods and resources
FRANK: a pan-cancer RNA-seq classifier for childhood tumors with data-efficient learning
FRANK, a neural network classifier for pan-cancer pediatric tumors, distinguishes 181 childhood tumor and normal tissue types from RNA-seq data. Trained on 11,467 curated transcriptomes with data augmentation and a hierarchical penalty, it detected tumor types from as few as three training examples and reached 98.3% overall accuracy across nine validation datasets totaling 16,398 samples. It outperformed other published pediatric pan-cancer RNA-seq classifiers on an external dataset and remained accurate on long-read, noisy and low-quality data.