bims-ovdlit 2025-04-13 papers

Nat Methods. 2025 Apr 11.

Error-corrected flow-based sequencing at whole-genome scale and its application to circulating cell-free DNA profiling.

Differentiating sequencing errors from true variants is a central genomics challenge, calling for error suppression strategies that balance costs and sensitivity. For example, circulating cell-free DNA (ccfDNA) sequencing for cancer monitoring is limited by sparsity of circulating tumor DNA, abundance of genomic material in samples and preanalytical error rates. Whole-genome sequencing (WGS) can overcome the low abundance of ccfDNA by integrating signals across the mutation landscape, but higher costs limit its wide adoption. Here, we applied deep (~120×) lower-cost WGS (Ultima Genomics) for tumor-informed circulating tumor DNA detection within the part-per-million range. We further leveraged lower-cost sequencing by developing duplex error-corrected WGS of ccfDNA, achieving 7.7 × 10-7 error rates, allowing us to assess disease burden in individuals with melanoma and urothelial cancer without matched tumor sequencing. This error-corrected WGS approach will have broad applicability across genomics, allowing for accurate calling of low-abundance variants at efficient cost and enabling deeper mapping of somatic mosaicism as an emerging central aspect of aging and disease.

DOI: https://doi.org/10.1038/s41592-025-02648-9

J Am Coll Surg. 2025 Apr 11.

A Role for General Surgery in Saving Lives from Ovarian Cancer.

Swathikan Chidambaram, Rebecca Stone, Kara Long Roche, Joseph V Sakran.

DOI: https://doi.org/10.1097/XCS.0000000000001409

Clin Cancer Res. 2025 Apr 08.

Navigating Complexity: Perspectives on Risk Assessment in the Era of New Blood-based Tests for Early Cancer Detection.

In recent years there has been a surge in the development of new, blood-based, single- and multi-cancer detection tests (SCD and MCD), which can detect cancer signals prior to the onset of symptoms or clinical diagnosis of cancer. Recognizing the need for consensus definitions and standardized evidence development frameworks for these new types of blood test, the Early Detection and Screening (ED&S) Working Group of the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative initiative dedicated to advancing standards and best practices, developed and published a lexicon for liquid-biopsy based SCD and MCD tests. During the preparation of the lexicon, the group recognized challenges regarding the definitions of key terms and concepts describing absolute and relative risk assessment of intended use populations for cancer screening tests. This article captures the working group's discussions on 1) risk assessment including considerations for adapting historical SCD risk terminology like "average risk" and "elevated risk" to MCD tests; 2) the implications of this terminology for describing intended use populations; 3) and the existing gaps in evidence for determination of absolute risks.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-4269

Nature. 2025 Apr 09.

Multimodal cell maps as a foundation for structural and functional genomics.

Human cells consist of a complex hierarchy of components, many of which remain unexplored1,2. Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. Self-supervised multimodal data integration resolves 275 molecular assemblies spanning the range of 10-8 to 10-5 m, which we validate systematically using whole-cell size-exclusion chromatography and annotate using large language models3. We explore key applications in structural biology, yielding structures for 111 heterodimeric complexes and an expanded Rag-Ragulator assembly. The map assigns unexpected functions to 975 proteins, including roles for C18orf21 in RNA processing and DPP9 in interferon signalling, and identifies assemblies with multiple localizations or cell type specificity. It decodes paediatric cancer genomes4, identifying 21 recurrently mutated assemblies and implicating 102 validated new cancer proteins. The associated Cell Visualization Portal and Mapping Toolkit provide a reference platform for structural and functional cell biology.

DOI: https://doi.org/10.1038/s41586-025-08878-3