Disruption of gene regulation is known to play major roles in carcinogenesis and tumour progression. Here, we comprehensively characterize the mutational profiles of diverse transcription factor binding sites (TFBSs) across 1,574 completely sequenced cancer genomes encompassing 11 tumour types. We assess the relative rates and impact of the mutational burden at the binding sites of 81 transcrip...

Analysis and comparison of mutational spectra represents a burning question in molecular biology. We report an algorithm based upon the SEM subclass approach (SEM--stochastique, estimations, maximizations). Any real mutational spectrum is regarded as a mixture of standard binomial distributions. The separation procedure is run by rounds. Each iteration includes simulation, maximization and esti...

Here we investigate how thermodynamic properties of orthologous proteins are influenced by the genomic environment in which they evolve. We performed a comparative computational study of 21 protein families in 73 prokaryotic species and obtained the following main results. (i) Protein stability with respect to the unfolded state and with respect to misfolding are anticorrelated. There appears t...

Recent large-scale genomic and evolutionary studies have revealed the small but detectable signature of weak selection on synonymous mutations during mammalian evolution, likely acting at the level of translational efficacy (i.e., translational selection). To investigate whether weak selection, and translational selection in particular, plays any role in shaping the fate of synonymous mutations...

Populations of individuals exist in a wide range of sizes, from billions of microorganisms to fewer than ten individuals in some critically endangered species saved on the brink of extinction. In any evolutionary system, there is significant evolutionary pressure to evolve sequences that are both fit and robust; at high mutation rates, individuals with greater mutational robustness can outcompe...

Intra-population heterogeneity is commonly observed in natural and cellular populations and has profound influence on their evolution. For example, intra-tumor heterogeneity is prevalent in most tumor types and can result in the failure of tumor therapy. However, the evolutionary process of heterogeneity remains poorly characterized at both genotypic and phenotypic level. Here we study the evol...

The pattern of mutational covariance among traits plays a central, but largely untested, role in many theories in evolutionary genetics. Here we estimate the pattern of phenotypic, environmental, and mutational correlations for a set of life-history, behavioral, and morphological traits using 67 self-fertilizing lines of Caenorhabditis elegans, each having independently experienced an average o...

Abstract Mutational signatures have emerged as powerful biomarkers in cancer patients, with prognostic and therapeutic implications. Wider clinical utility requires access to reproducible algorithms, which allow characterization of mutational a given tumor sample. Here, we show how signature fitting can be applied hematological genomes identify biologically clinically important processes, highl...