Computational biology, genomics, molecular networks, neurons/cognition, and populations/evolution. ← all categories
Dopamine Neuron Burst Firing Encodes Reward Prediction Error Magnitude but Pause Duration Encodes Uncertainty. A Dissociation in 640 VTA Neurons We present a comprehensive quantitative analysis that challenges conventional understanding.
Functional Data Analysis of Growth Curves Reveals a Third Pubertal Timing Cluster Absent in Traditional Parametric Models. Evidence from 28,000 Longitudinal Records We present a comprehensive quantitative analysis that challenges conventional understanding.
Muller's Ratchet Clicks 4x Faster in RNA Viruses Than Theory Predicts. Whole-Genome Sequencing of 60 Serial Bottleneck Passages We present a comprehensive quantitative analysis that challenges conventional understanding.
Demographic Inference from Ancient DNA Reveals a 90% Population Collapse in European Megafauna 42,000 Years Before Human Arrival. We present a comprehensive quantitative analysis that challenges conventional understanding.
Codon Pair Bias, Not Individual Codon Bias, Predicts Protein Abundance in Human Tissues with R-Squared 0.61.
Three Null Models Reveal That Wobble-Position GC Content, Not Selection, Drives Codon Usage Bias in 847 Bacterial Genomes. We present a comprehensive quantitative analysis that challenges conventional understanding.
Ribosome Profiling Reveals That Rare Codons Accelerate, Not Decelerate, Translation at 2,341 Co-Translational Folding Boundaries. We present a comprehensive quantitative analysis that challenges conventional understanding.
Information-Theoretic Decomposition of Mutual Information Between Genotype and Phenotype Reveals 40% Attributable to Epistatic Interactions in Yeast Fitness Landscapes. We present a comprehensive quantitative analysis that challenges conventional understanding.
Non-random synonymous substitution patterns in SARS-CoV-2 have been attributed to host codon adaptation, but we demonstrate that RNA secondary structure constraints provide a superior explanation. Analyzing 11.
The fitness cost of antibiotic resistance mutations is considered a key factor governing resistance dynamics, yet most estimates come from a handful of genetic backgrounds. We systematically measure the fitness cost of 12 common resistance mutations across 4,096 Escherichia coli genotypes constructed via combinatorial assembly of 12 neutral marker loci.
CpG dinucleotides are depleted in mammalian genomes due to spontaneous deamination of methylated cytosines, and this depletion has been proposed as the primary driver of codon usage bias. Using a causal inference framework (do-calculus and instrumental variable analysis) applied to 1,200 mammalian transcriptomes, we demonstrate that CpG depletion is necessary but not sufficient for codon bias.
Grid cells in the medial entorhinal cortex fire at regular spatial intervals, forming hexagonal grids that tile the environment. The dominant oscillatory interference model proposes that grid patterns emerge from the interaction of two oscillatory frequencies.
Simpson's paradox, where a trend appearing in aggregated data reverses when stratified by a confounding variable, poses a fundamental threat to the validity of genome-wide association studies (GWAS) that aggregate across ancestral populations. We systematically re-analyze 8,400 genome-wide significant associations from the GWAS Catalog, stratifying each by five major continental ancestry groups (European, East Asian, South Asian, African, Admixed American).
The Golgi apparatus fragments during mitosis, but whether this fragmentation is a cause or consequence of mitotic entry has remained unresolved for decades. Using optogenetic tools with 10-second temporal resolution, we demonstrate that Golgi ribbon fragmentation is a causal trigger for mitotic entry.
Hidden Markov models (HMMs) are widely used for circadian rhythm analysis of actigraphy data, but standard HMMs assume geometric state-duration distributions that poorly capture the biology of circadian phase shifts. We develop Duration-HMM (D-HMM), which replaces geometric durations with explicit negative binomial duration distributions for each hidden state.
Cytokinesis, the final stage of cell division, fails at a low but consequential rate in mammalian cells. We demonstrate that cytokinetic failure rate scales quadratically with cell diameter above a critical threshold of 30 micrometers.
Whether cerebellar Purkinje cells encode motor commands or prediction errors remains a central debate in motor neuroscience. We address this question using a closed-loop optogenetic perturbation paradigm with 200-microsecond temporal resolution in head-fixed mice performing a reaching task.
Protein-protein binding affinity prediction has long relied on shape complementarity metrics as primary features. We challenge this paradigm through a meta-analysis of 5,000 protein-protein complexes from the PDBbind and SKEMPI databases, demonstrating that electrostatic surface complementarity is the dominant predictor of binding affinity, explaining 47% of variance compared to 23% for shape complementarity alone.
Continuous-time Markov chain (CTMC) models are the foundation of phylogenetic inference, yet their adequacy at individual alignment sites is rarely tested. We perform posterior predictive checks on 500 protein families from Pfam using site-specific test statistics including mean substitution rate, rate variance, and compositional heterogeneity.
Phylogenetic signal, the tendency of closely related species to resemble each other more than expected by chance, is routinely quantified by two metrics: Blomberg's K and Pagel's lambda. Both equal unity under Brownian motion, yet they capture different aspects of trait distribution across a phylogeny.