Related papers: Genetic variation in human drug-related genes
Genetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect,…
Predicting drug responses using genetic and transcriptomic features is crucial for enhancing personalized medicine. In this study, we implemented an ensemble of machine learning algorithms to analyze the correlation between genetic and…
The genes that encode the targets of most therapies do not have rare variants with large-effect or common variants with moderate effects on the biomarker reflecting the pharmacologic action of the corresponding therapy. Therefore, providing…
Although somatic mutations are the main contributor to cancer, underlying germline alterations may increase the risk of cancer, mold the somatic alteration landscape and cooperate with acquired mutations to promote the tumor onset and/or…
Our genomes influence nearly every aspect of human biology from molecular and cellular functions to phenotypes in health and disease. Human genetics studies have now associated hundreds of thousands of differences in our DNA sequence…
Cancer cell lines have frequently been used to link drug sensitivity and resistance with genomic profiles. To capture genomic complexity in cancer, the Cancer Genome Project (CGP) (Garnett et al., 2012) screened 639 human tumor cell lines…
The emergence of acquired drug resistance in cancer represents a major barrier to treatment success. While research has traditionally focused on genetic sources of resistance, recent findings suggest that cancer cells can acquire transient…
Individual cancer cells carry a bewildering number of distinct genomic alterations i.e., copy number variations and mutations, making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here we performed…
We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher…
The study of high-throughput genomic profiles from a pharmacogenomics viewpoint has provided unprecedented insights into the oncogenic features modulating drug response. A recent screening of ~1,000 cancer cell lines to a collection of…
It is increasingly common clinically for cancer specimens to be examined using techniques that identify somatic mutations. In principle these mutational profiles can be used to diagnose the tissue of origin, a critical task for the 3-5% of…
Identifying drivers of complex traits from the noisy signals of genetic variation obtained from high throughput genome sequencing technologies is a central challenge faced by human geneticists today. We hypothesize that the variants…
Drug resistance remains a major problem for the treatment of HIV. Resistance can occur due to mutations that were present before treatment starts or due to mutations that occur during treatment. The relative importance of these two sources…
Non-genetic forms of antimicrobial drug resistance can result from cell-to-cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non-genetic mechanisms can facilitate the development of…
Identifying genes associated with complex human diseases is one of the main challenges of human genetics and computational medicine. To answer this question, millions of genetic variants get screened to identify a few of importance. To…
Predicting the response of a specific cancer to a therapy is a major goal in modern oncology that should ultimately lead to a personalised treatment. High-throughput screenings of potentially active compounds against a panel of genomically…
The majority of common diseases are influenced by multiple genetic and environmental factors such as Cancer. Even though uncovering the main causes of disease is deemed difficult due to the complexity of gene-gene and gene-environment…
Advances in sequencing have revealed that each individual carries about 10,000 missense variants. For the vast majority, we do not know what the functional consequences - if any - will be. Further, mechanistic insight, such as structural…
The depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical…
Genetic mutations can cause disease by disrupting normal gene function. Identifying the disease-causing mutations from millions of genetic variants within an individual patient is a challenging problem. Computational methods which can…