Related papers: Genetic variation in human drug-related genes
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…
Evolutionary dynamics and patterns of molecular evolution are strongly influenced by selection on linked regions of the genome, but our quantitative understanding of these effects remains incomplete. Recent work has focused on predicting…
A principal component analysis of the TCGA data for 15 cancer localizations unveils the following qualitative facts about tumors: 1) The state of a tissue in gene expression space may be described by a few variables. In particular, there is…
Many common diseases are highly polygenic, modulated by a large number genetic factors with small effects on susceptibility to disease. These small effects are difficult to map reliably in genetic association studies. To address this…
The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML…
Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies of cancer cells have shown that the mutational landscape of cancer is complex and that individual cancers…
Variant calling, the problem of estimating whether a position in a DNA sequence differs from a reference sequence, given noisy, redundant, overlapping short sequences that cover that position, is fundamental to genomics. We propose a deep…
Resistance to chemotherapies, particularly to anticancer treatments, is an increasing medical concern. Among the many mechanisms at work in cancers, one of the most important is the selection of tumor cells expressing resistance genes or…
Predicting the efficacy of a drug for a given individual, using high-dimensional genomic measurements, is at the core of precision medicine. However, identifying features on which to base the predictions remains a challenge, especially when…
Large populations may contain numerous simultaneously segregating polymorphisms subject to natural selection. Since selection acts on individuals whose fitness depends on many loci, different loci affect each other's dynamics. This leads to…
Cancer and healthy cells have distinct distributions of molecular properties and thus respond differently to drugs. Cancer drugs ideally kill cancer cells while limiting harm to healthy cells. However, the inherent variance among cells in…
Mutated genes may lead to cancer development in numerous tissues. While more than 600 cancer-causing genes are known today, some of the most widespread mutations are connected to the RAS gene: RAS mutations are found in approximately 25% of…
In the search for genetic factors that are associated with complex heritable human traits, considerable attention is now being focused on rare variants that individually have small effects. In response, numerous recent papers have proposed…
Immunotherapy has recently shown important clinical successes in a substantial number of oncology indications. Additionally, the tumor somatic mutation load has been shown to associate with response to these therapeutic agents, and specific…
Finding tumour genetic markers is essential to biomedicine due to their relevance for cancer detection and therapy development. In this paper, we explore a recently released dataset of chromosome rearrangements in 2,586 cancer patients,…
The observation that phenotypic variability is ubiquitous in isogenic populations has led to a multitude of experimental and theoretical studies seeking to probe the causes and consequences of this variability. Whether it be in the context…
Genetically identical cells in the same population can take on phenotypically variable states, leading to differentiated responses to external signals, such as nutrients and drug-induced stress. Many models and experiments have focused on a…
How do we determine the mutational effects in exome sequencing data with little or no statistical evidence? Can protein structural information fill in the gap of not having enough statistical evidence? In this work, we answer the two…
A biological transition from a state N to a state T is characterized by a rearrangement of the gene expression profile in the system, quantitatively measured through the differential expression of genes. In contrast, changes in genetic…
Polygenic risk scores (PRSs) can significantly enhance breast cancer risk prediction when combined with clinical risk factor data. While many studies have explored the value-add of PRSs, little is known about the potential impact of…