Biology subjects

We

Publications and source records attributed to We.

3 recordsLinked to original sources

bioRxiv2026

A complete human pancreatic cancer genome

Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine.1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions.1-3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres.4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

genomics↗

bioRxiv2025

Globally unified analysis of riverine eDNA reveals common associations of fish biodiversity with drainage characteristics

Freshwater biodiversity is declining at a pace that outstrips the capacity of existing monitoring approaches both in temporal and spatial dimensions, highlighting the urgent need for rapid and scalable assessment and attribution of biodiversity states and changes. Here, we present one of the first global assessments and unified analyses of riverine fish biodiversity using environmental DNA (eDNA) collected from 1818 sites across 113 river systems. We quantified species richness, functional redundancy, phylogenetic diversity, and genetic sequence diversity, and related them to drainage characteristics. Our results showed that eDNA effectively captured global patterns of multi-faceted riverine fish biodiversity and disentangled the roles of climate and human activities in shaping biodiversity-area relationships. Catchments in warmer climates consistently enhanced biodiversity accumulation with area, while higher human activity intensity weakened this scaling. Species richness, functional, and genetic sequence diversity exhibited stronger negative responses to human activities in larger catchments. In contrast, phylogenetic diversity showed the strongest negative effects in smaller catchments with these impacts diminishing as catchment area increased, highlighting the facet-dependent nature of biodiversity responses to environmental gradients. Our findings demonstrate the power of eDNA-based datasets for harmonized, multi-faceted biodiversity assessments, offering a scalable approach for detecting and attributing biodiversity change and informing conservation strategies under accelerating global change.

ecology↗

bioRxiv2023

Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera

The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.

bioinformatics↗