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Biology subjects

Sanger, T.

Publications and source records attributed to Sanger, T..

3 recordsLinked to original sources

BACE: Behavior-Adaptive Connectivity Estimation for Interpretable Graphs of Neural Dynamics

Understanding how distributed brain regions coordinate to produce behavior requires models that are both predictive and interpretable. We introduce Behavior-Adaptive Connectivity Estimation (BACE), an end-to-end framework that learns phase-specific, directed inter-regional connectivity directly from multi-region intracranial local field potentials (LFP). BACE aggregates many micro-contacts within each anatomical region via per-region temporal encoders, applies a learnable adjacency specific to each behavioral phase, and is trained on a forecasting objective. On synthetic multivariate time series with known graphs, BACE accurately recovers ground-truth directed interactions while achieving forecasting performance comparable to state-of-the-art baselines. Applied to human subcortical LFP recorded simultaneously from eight regions during a cued reaching task, BACE yields an explicit 8x8 connectivity matrix for each within-trial behavioral phase. The resulting behavioral phase-specific graphs reveal behavioraligned reconfiguration of inter-regional influence and provide compact, interpretable adjacency matrices for comparing network organization across behavioral phases. By linking predictive success to explicit connectivity estimates, BACE offers a practical tool for generating data-driven hypotheses about the dynamic coordination of subcortical regions during behavior.

neuroscience↗

On the causes, consequences, and avoidance of PCR duplicates: towards a theory of library complexity

AO_SCPLOWBSTRACTC_SCPLOWLibrary preparation protocols for most sequencing technologies involve PCR amplification of the template DNA, which open the possibility that a given template DNA molecule is sequenced multiple times. Reads arising from this phenomenon, known as PCR duplicates, inflate the cost of sequencing and can jeopardize the reliability of affected experiments. Despite the pervasiveness of this artifact, our understanding of its causes and of its impact on downstream statistical analyses remains essentially empirical. Here, we develop a general quantitative model of amplification distortions in sequencing datasets, which we leverage to investigate the factors controlling the occurrence of PCR duplicates. We show that the PCR duplicate rate is determined by the ratio between library complexity and sequencing depth, and that amplification noise (including in its dependence on the number of PCR cycles) only plays a minor role for this artifact. We confirm our predictions using new and published RAD-seq libraries and provide a method to estimate library complexity and amplification noise in any dataset containing PCR duplicates. We discuss how amplification-related artifacts impact downstream analyses, and in particular genotyping accuracy. The proposed framework unites the numerous observations made on PCR duplicates and will be useful to experimenters of all sequencing technologies where DNA availability is a concern.

molecular biology↗

Evidence against tetrapod-wide digit identities and for a limited frame shift in bird wings

In crown group tetrapods, individual digits are homologized in relation to a pentadactyl ground plan. However, testing hypotheses of digit homology is challenging because it is unclear whether digits develop with distinct and conserved gene regulatory states. Here we show dramatic evolutionary dynamism in the gene expression profiles of digits, challenging the notion that five digit identities are conserved across amniotes. Transcriptomics of developing limbs shows diversity in the patterns of genetic differentiation of digits, although the anterior-most digit of the pentadactyl limb has a unique, conserved expression profile. Further, we identify a core set of transcription factors that are differentially expressed among the digits of amniote limbs; their spatial expression domains, however, vary between species. In light of these results, we reevaluate the frame shift hypothesis of avian wing evolution and conclude that only the identity of the anterior-most digit has shifted position, suggesting a 1,3,4 digit identity in the bird wing.

evolutionary biology↗