bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.26.761332

CNVSIM: an interpretable copy-number reference atlas for cancer subtyping

YU, J.·Bardet-Trouilloud, J.·Jaeger, S.·Baudis, M.
View original source ↗Export metadata ↓

Abstract

Background: Genome-wide copy-number variation (CNV) profiles provide a structural representation of cancer genomes, but interpreting new profiles within a reusable reference remains challenging. Results: We developed CNVSIM, which organizes CNV profiles into cancer root-specific reference spaces and defines reference subtypes annotated with chromosome-scale and gene-level signatures. Applied to the Progenetix dataset, CNVSIM established 112 CNV-defined subtypes across 19 cancer roots, supported by 155,881 analyses from neoplastic samples. Within each cancer root, samples sharing a broad diagnosis separated into distinct CNV subtypes, whereas individual subtypes spanned multiple diagnostic labels. All subtypes included analyses from multiple assay platforms and data sources, and core subtypes remained reproducible after systematic reduction of reference analyses. Calibrated projection assigned 85.7% of held-out CNV profiles while maintaining high accuracy for supported assignments. Projection of 4,605 cell-line CNV profiles identified cell lines representative for 90/112 cancer subtypes while highlighting gaps in cell line representation. Conclusions: CNVSIM provides a reusable and interpretable CNV reference that complements diagnostic classification for profile comparison, projection, and cell line selection.

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

YU, J., Bardet-Trouilloud, J., Jaeger, S., Baudis, M.. 2026-10-30. CNVSIM: an interpretable copy-number reference atlas for cancer subtyping. https://doi.org/10.64898/2026.10.26.761332

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

An invariant network architecture with broadly expressed regulators distinguishes cell-type from cell-state identity in situ

Core regulatory networks (CRNs) of tissue-specific master transcription factors (TFs) are essential for defining cell identity and are widely used to reprogram cells and to decipher pathogenic mechanisms. However, to date, CRNs have only been described at the cell-type level: their characteristics in the distinct states that a single cell type can adopt have not been examined. This leaves open what the cell-type CRNs actually represent. Here, using the zonated hepatocyte states of the mouse liver as a model system, we construct the first state-level CRNs in a native tissue. For this purpose, we developed a robust LCM-Spatial-ATAC-seq method that achieves bulk-level data quality from microdissected cell populations. By identifying what is shared among the state-level CRNs, we determined what is cell-type defining: an invariant sub-network of core-regulatory TFs (crTFs) that maintains identical positions and conserved interactions in the CRNs. Unexpectedly, the top positions of this invariant sub-network are occupied by broadly expressed TFs rather than the well-established master TFs, which reside downstream. Yet the state-level CRNs are clearly different, both in terms of composition and interactions. The former are dominated by zone-specific regulators, whereas the latter are spread throughout the network, encompassing about one third of all interactions between the states. Thus, our results reveal a novel dual character of a cell's CRN: an invariant sub-network that defines the cell-type identity, together with a variable peripheral network that underlies its state specialization.

genomics↗
bioRxiv2026

Towards a complete diploid chicken genome

The repetitive and heterochromatic parts of microchromosomes and dot chromosomes have impeded the creation of a complete, haplotype-resolved chicken genome. To overcome these challenges, we employed a trio-sequencing approach, utilizing long reads from a female chick, supplemented by parental long-read data for accurate haplotype phasing. This strategy produced nearly complete, haplotype-resolved paternal and maternal assemblies, with 14 residual gaps. Telomeric sequences remain missing in two paternal and four maternal chromosomes, suggesting a still incomplete assembly. GGswu2 resolved more than 50 Mb of previously unresolved regions, predominantly within dot chromosomes. The dot chromosomes exhibit low nucleotide diversity but a high density of structural variants between haplotypes. We found that the centromere sizes and relative positions of centromere cores sometimes differ between the two haplotype genomes. These findings suggest that comparative genomics must incorporate the high-resolution of these dynamic complex regions to fully understand avian genome evolution and genetic complexity.

genomics↗
bioRxiv2026

Venom toxin genes are tandem-arrayed beyond gene-family-size expectations in four venomous bilaterian species

Toxin genes of venomous animals often lie in tandem arrays, but large gene families cluster whatever their function, so how much of this architecture is specific to toxins is unclear. We asked whether toxin genes cluster more than non-toxin gene families of the same size and, if so, what carries the excess. Across five venomous genomes, anchored on a new chromosome-level genome of the centipede Scolopendra mutilans with a 12-individual venom-gland proteome, the clustering enrichment of toxin genes fell from 14-31-fold against random genes to about 2-6-fold against size-matched non-toxin families in the four bilaterian species (centipede, snake, spider, scorpion), but did not disappear: the matched odds ratio remained above 1 across three gene-family definitions and, under the primary definition, windows of 25-200 kb, matching on within-family sequence similarity and, in the snake, a published venom-gene annotation, whereas evidence in the sea anemone was insufficient to establish an excess. The excess was spread across many toxin families and was carried mainly by homologous copies lying next to one another. In evaluable families, phylogenetically closest copies were physically closer than their families' layout predicts in toxin and non-toxin tandem families alike; tandem toxin copies did not differ detectably in expression output; and a pre-specified congener comparison had too little information to be evaluated. Toxin genes are thus tandem-arrayed beyond family-size expectations in the four sampled bilaterian species, and the excess lies mainly in homologous arrays; the present comparisons do not distinguish whether such arrays form more often or persist longer.

genomics↗