Related papers: Genetic variation in human drug-related genes
The rise of single-cell sequencing technologies has revolutionized the exploration of drug resistance, revealing the crucial role of cellular heterogeneity in advancing precision medicine. By building computational models from existing…
Motivation: Predicting the metastatic potential of primary malignant tissues has direct bearing on choice of therapy. Several microarray studies yielded gene sets whose expression profiles successfully predicted survival (Ramaswamy et al…
With declining sequencing costs a promising and affordable tool is emerging in cancer diagnostics: genomics. By using association studies, genomic variants that predispose patients to specific cancers can be identified, while by using tumor…
In cancer genomics, it is of great importance to distinguish driver mutations, which contribute to cancer progression, from causally neutral passenger mutations. We propose a random-effect regression approach to estimate the effects of…
When genetic variants in a gene cluster are associated with a disease outcome, the causal pathway from the variants to the outcome can be difficult to disentangle. For example, the chemokine receptor gene cluster contains genetic variants…
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 pathogenesis of cancer in human is still poorly understood. With the rapid development of high-throughput sequencing technologies, huge volumes of cancer genomics data have been generated. Deciphering those data poses great…
Cancer prognosis can be regarded as estimating the risk of future outcomes from multiple variables. In prognostic signatures, these variables represent expressions of genes that are summed up to calculate a risk score. However, it is a…
The possibility of targeting the causal genes along with the mechanisms of pathogenically complex diseases has led to numerous studies on the genetic etiology of some diseases. In particular, studies have added more genes to the list of…
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…
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
Drug development is a very costly and lengthy process, while repositioned or repurposed drugs could be brought into clinical practice within a shorter time-frame and at a much reduced cost. The past decade has observed a massive growth in…
The goal of eQTL studies is to identify the genetic variants that influence the expression levels of the genes in an organism. High throughput technology has made such studies possible: in a given tissue sample, it enables us to quantify…
This Perspective provides examples of current and future applications of deep learning in pharmacogenomics, including: (1) identification of novel regulatory variants located in noncoding domains and their function as applied to…
In medical genetics, each genetic variant is evaluated as an independent entity regarding its clinical importance. However, in most complex diseases, variant combinations in specific gene networks, rather than the presence of a particular…
Identifying genes underlying cancer development is critical to cancer biology and has important implications across prevention, diagnosis and treatment. Cancer sequencing studies aim at discovering genes with high frequencies of somatic…
Opioids are an effective analgesic for acute and chronic pain, but also carry a considerable risk of addiction leading to millions of opioid use disorder (OUD) cases and tens of thousands of premature deaths in the United States yearly.…
A mutation in a protein-coding gene in DNA can alter the protein structure coded by the same gene. Structurally altered proteins usually lose their functions and sometimes gain an undesirable function instead. These types of mutations and…
In population genetics, mutation rate is often treated as a homogeneous parameter across the genome. Empirical evidence, however, shows systematic variation across genomic contexts associated with chromatin organization and epigenomic…
An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…