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Oct 11Sun
  1. biorxiv.org59

    From APTs to advanced persistent biological threats (APBTs): a taxonomy and large-scale metadata audit of genomic surveillance infrastructure

    Every one of 100,000 audited SARS-CoV-2 BioSample records from NCBI triggered at least one APBT-relevant metadata vulnerability indicator, with a mean of 7.34 indicators per record, and 97.3% fell into High or Critical severity. The audit applied 23 checks across five metadata layers within a new four-phase taxonomy of Advanced Persistent Biological Threats. The gaps stem largely from optional fields in the BioSample submission model, meaning poisoned or weakly traceable metadata could plausibly enter surveillance pipelines undetected.

  2. biorxiv.org68

    Disrupted chromatin architecture blocks B lymphopoiesis in Down syndrome

    Three-dimensional genome architecture organizes human fetal haematopoiesis and explains the B-lineage defect in Down syndrome. Using ChromE-seq, a new single-cell assay jointly profiling chromatin conformation and transcription, the authors built a multimodal atlas of ~400,000 haematopoietic cells from disomic and trisomy 21 fetal liver. Trisomy 21 disproportionately disrupted B-lineage architecture, weakened an EBF1-centred regulatory circuit, and deleting a T21-sensitive EBF1 loop anchor reproduced the CLP-to-B-progenitor bottleneck seen in T21.

    Why it matters: Links 3D chromatin architecture to lineage priming and identifies an EBF1 circuit behind the trisomy 21 B-cell defect.

  3. biorxiv.org71

    Massively scaled variant effect mapping across the MAPK pathway reveals the importance of molecular and cellular context

    Variant effect mapping of 186,676 variants across 17 RAS-MAPK pathway proteins in human cells, totaling 503,099 measurements of protein abundance and pathway activity, revealed 14,412 dominant negative variants across 12 proteins, nearly all previously unknown and depleted from the human population. HSP90 inhibition experiments showed HSP90 shapes the effect of 67% of missense variants across the pathway. The data also resolved how the KRAS switch II helix surface accommodates overlapping LZTR1 and SOS1 interactions through distinct allosteric networks.

    Why it matters: Because it shows cellular context, especially HSP90, shapes the effect of most variants in a core signaling pathway.

Oct 9Fri
  1. biorxiv.org65

    The Red Blood Cell Surface Defines a Distinct Tumor DNA Compartment for Liquid Biopsy

    Red blood cells tether and retain tumor-derived DNA on their surface, forming a distinct circulating pool of RBC-bound tumor DNA (rtDNA), with desialylation increasing capture in a Toll-like receptor 9-dependent manner. In mice bearing lung cancer xenografts, rtDNA was detected in all animals and tracked tumor burden while plasma tumor DNA was undetectable; in patients with lung cancer, most detected mutant tumor DNA was RBC-associated and concordant with matched tumor tissue. The findings challenge the plasma-centric liquid biopsy paradigm by identifying the RBC surface as a tunable reservoir of tumor DNA.

    Why it matters: It identifies red blood cells, not plasma, as the main circulating compartment of tumor DNA for liquid biopsy.

Oct 7Wed
  1. nature.com82

    RNA catalysis emerges from dynamic structural ensembles

    A heterogeneity-focused cryo-EM workflow resolves the conformational landscape of Geobacillus stearothermophilus RNase P RNA at near-atomic resolution, with and without the protein component rnpA, and maps structural and catalytic Mg2+ ions directly. More than 80% of the ribozyme's residues are flexible under physiological Mg2+ concentrations, a heterogeneity that static structures could not explain. Simulations estimate at least 50,000 particles are needed for a roughly 3 Å volume of this RNA. The work links RNA conformational dynamics to catalytic activity and provides a framework for studying flexible RNAs and their ions.

    Why it matters: It visualizes RNA conformational ensembles and Mg2+ ion dynamics at near-atomic resolution, which static methods could not capture.

Oct 6Tue
  1. biorxiv.org46

    Disease-associated mutations directionally modulate epigenetic age in iPSC-derived tissues

    Epigenetic age progressively increases with serial passaging of iPSC-derived lung organoids (alveolospheres), measured by multiple epigenetic clock models, providing a reproducible in-vitro way to re-establish aging trajectories lost at reprogramming. Disease-associated mutations added cell-intrinsic shifts in epigenetic age across multiple models, marking disease state as an independent modulator of epigenetic clocks. The work extends iPSC systems to modeling age-associated cellular states beyond genetics.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org