Related papers: The Impact of Genomic Variation on Function (IGVF)…
There is an intrinsic relationship between the molecular evolution in primordial period and the properties of genomes and proteomes of contemporary species. The genomic data may help us understand the driving force of evolution of life at…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate genes. In this perspective,…
Correlation of gene histories in the human genome determines the patterns of genetic variation (haplotype structure) and is crucial to understanding genetic factors in common diseases. We derive closed analytical expressions for the…
With the surge in the number of variants of uncertain significance (VUS) reported in ClinVar in recent years, there is an imperative to resolve VUS at scale. Multiplexed assays of variant effect (MAVEs), which allow the functional…
High-throughput genetic and epigenetic data are often screened for associations with an observed phenotype. For example, one may wish to test hundreds of thousands of genetic variants, or DNA methylation sites, for an association with…
Phylogenetic analyses of gene expression have great potential for addressing a wide range of questions. These analyses will, for example, identify genes that have evolutionary shifts in expression that are correlated with evolutionary…
Despite the wealth of single-cell multi-omics data, it remains challenging to predict the consequences of novel genetic and chemical perturbations in the human body. It requires knowledge of molecular interactions at all biological levels,…
To date, genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants among a variety of traits/diseases, shedding a light on the genetic architecture of complex diseases. Polygenicity of complex…
Trisomy, a form of aneuploidy wherein the cell possesses an additional copy of a specific chromosome, exhibits a high correlation with cancer. Studies from across different hosts, cell-lines, and labs into the cellular effects induced by…
Genome-wide association studies (GWAS) have identified hundreds of loci at very stringent levels of statistical significance across many different human traits. However, it is now clear that very large samples (n~10^4-10^5) are needed to…
Genetic association data from national biobanks and large-scale association studies have provided new prospects for understanding the genetic evolution of complex traits and diseases in humans. In turn, genomes from ancient human…
In the past decade, advances in genome sequencing have allowed researchers to uncover the history of hybridization in diverse groups of species, including our own. Although the field has made impressive progress in documenting the extent of…
Scientists have been trying to identify all of the genes in the human genome since the initial draft of the genome was published in 2001. Over the intervening years, much progress has been made in identifying protein-coding genes, and the…
Characterizing non-coding variant function remains an important challenge in human genetics. Genomic deep learning models have emerged as a promising approach to enable in silico prediction of variant effects. These include supervised…
In genetic association studies, detecting phenotype-genotype association is a primary goal. We assume that the relationship between the data -phenotype, genetic markers and environmental covariates - can be modelled by a generalized linear…
The genotype-phenotype map is an essential object in our understanding of organismal complexity and adaptive properties, determining at once genomic plasticity and those constraints that may limit the ability of genomes to attain…
Complexity in biology is often described using a multi-map architecture, where the genotype, representing the encoded information, is mapped to the functional level, known as the phenotype, which is then connected to a latent phenotype we…
The effect of genetic operators other than selection, such as mutation and recombination, on the genotype-phenotype map is considered. In particular, when the genotypic fitness landscape exhibits a ``symmetry'', i.e. many genotypes…
Despite significant progress in dissecting the genetic architecture of complex diseases by genome-wide association studies (GWAS), the signals identified by association analysis may not have specific pathological relevance to diseases so…