Frost, N. | Search bioRxiv

bioRxiv2026

Copy number signatures in targeted gene panels associate with patient outcomes in routine clinical data

Targeted gene panels (TGPs) dominate clinical sequencing, yet most copy-number (CN) signature studies rely on genome-wide assays. Whether signatures can be recovered from TGPs and retain clinical relevance remains unclear. We analyzed two real-world TGP cohorts comprising 1,726 patients across 62 tumor types, including 825 with clinical annotations, and made the underlying data publicly available. TGP-derived signatures recapitulated established biological associations, including links to homologous recombination deficiency and TP53 alterations, concordant with published genome-wide assay-derived CN signatures. Using our detailed clinical data, we found TGP-derived CN signatures associated with overall survival under standard therapies in ovarian, pancreatic, and colorectal cancer. In ovarian cancer, CN2 was associated with CCNE1 amplification and shorter survival under paclitaxel/carboplatin, with the survival association validated in an independent SNP-array cohort. These findings demonstrate that routine TGPs yield biologically and clinically relevant CN signatures with potential as biomarkers for therapy stratification.

genetics↗

bioRxiv2020

Dynamic correlations help prefrontal ensembles transmit information about social behavior

New technologies have made it possible to measure activity from many neurons simultaneously. Nevertheless, most studies still analyze the activity of simultaneously recorded neurons one-at-a-time, then group together neurons which increase their activity during similar behaviors into an ensemble. This notion of an ensemble ignores the ability of neurons to act collectively, and encode and transmit information in ways that are not reflected by their individual activity levels. We used microendoscopic GCaMP imaging to measure prefrontal activity while mice were either alone or engaged in social interaction. We developed new approaches, using neural network classifiers and surrogate (shuffled) datasets, to characterize how neurons synergistically transmit information about social behavior. Surrogate datasets which preserve behaviorally-specific patterns of coactivity (correlations) outperform those which preserve behaviorally-driven changes in activity levels but not correlated activity. This shows that prefrontal neurons act collectively to transmit information about socialization, because social behavior elicits increases in correlated activity that are not explained simply by the activity levels of the underlying neurons. Notably, this ability of correlated activity to enhance the information transmitted by neuronal ensembles is lost in mice lacking the autism-associated gene Shank3. These results show that synergy is an important concept for the coding of social behavior which can be disrupted in disease states, reveal a specific mechanism underlying this synergy (social behavior increases correlated activity within specific ensembles), and outlines methods for studying how neurons within an ensemble can work together to encode information.

neuroscience↗