Related papers: Neutral genetic drift can aid functional protein e…

Designing protein mutants of both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants of improved stability and activity…

The two strands of a DNA molecule with a repetitive sequence can pair into many different basepairing patterns. For perfectly periodic sequences, early bulk experiments of Poerschke indicate the existence of a sliding process, permitting…

Computational methods are needed to differentiate the small fraction of missense mutations that contribute to disease by disrupting protein function from neutral variants. We describe several complementary methods using large-scale homology…

Classical population genetics a priori assigns fitness to alleles without considering molecular or functional properties of proteins that these alleles encode. Here we study population dynamics in a model where fitness can be inferred from…

Cancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the…

The standard genetic code is well known to be optimized for minimizing the phenotypic effects of single nucleotide substitutions, a property that was likely selected for during the emergence of a universal code. Given the fitness advantage…

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Stochasticity is both exploited and controlled by cells. Although the intrinsic stochasticity inherent in biochemistry is relatively well understood, cellular variation, or 'noise', is predominantly generated by interactions of the system…

Stochastic oscillations in individual cells are usually characterized by a non-monotonic power spectrum with an oscillatory autocorrelation function. Here we develop an analytical approach of stochastic oscillations in a minimal hybrid…

Mutations in proteins can have deleterious effects on a protein's stability and function, which ultimately causes particular diseases. Genetically inherited muscular dystrophies (MDs) include several genetic diseases, which cause increasing…

Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the probability of multi-mutation leaps, that is, several mutations…

Post-translational modification (PTM) of proteins plays a key role in signal transduction, and hence significant effort has gone toward understanding how PTM networks process information. This involves, on the theory side, analyzing the…

Protein fitness landscapes frequently exhibit epistasis, where the effect of a mutation depends on the genetic context in which it occurs, i.e., the rest of the protein sequence. Epistasis increases landscape complexity, often resulting in…

Robustness to genetic or environmental disturbances is often considered as a key property of living systems. Yet, in spite of being discussed since the 1950s, how robustness emerges from the complexity of genetic architectures and how it…

Motivation: Since susceptibility to diseases increases with age, studying aging gains importance. Analyses of gene expression or sequence data, which have been indispensable for investigating aging, have been limited to studying genes and…

Identifying the complete set of functional elements within the human genome would be a windfall for multiple areas of biological research including medicine, molecular biology, and evolution. Complete knowledge of function would aid in the…

Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…

Biological functions are typically performed by groups of cells that express predominantly the same genes, yet display a continuum of phenotypes. While it is known how one genotype can generate such non-genetic diversity, it remains unclear…

The possibility that the sliding motion of proteins on DNA is influenced by the base sequence through a base pair reading interaction, is considered. Referring to the case of the T7 RNA-polymerase, we show that the protein should follow a…

The choice of crossover and mutation strategies plays a crucial role in the searchability, convergence efficiency and precision of genetic algorithms. In this paper, a novel improved genetic algorithm is proposed by improving the crossover…