Related papers: Genetic variation in human drug-related genes
The discovery of genetic risk factors has transformed human genetics, yet the pace of new gene identification has slowed despite the exponential expansion of sequencing and biobank resources. Current approaches are optimized for the…
Deleterious genetic variants can be evaluated as quantitative traits using information theory-based sequence analysis of recognition sites. To assess the effect of such variants, fitness and genetic load of SNPs which alter binding site…
Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be…
Numerous challenges persist that delay clinical interpretation of human genetic variants, to name a few: (1) un- structured PubMed articles are the most abundant source of evidence, yet their variant annotations are difficult to query…
Variability is ubiquitous in nature and a fundamental feature of complex systems. Few studies, however, have investigated variance itself as a trait under genetic control. By focusing primarily on trait means and ignoring the effect of…
Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade. Multi-target drugs…
Large variability between cell lines brings a difficult optimization problem of drug selection for cancer therapy. Standard approaches use prediction of value for this purpose, corresponding e.g. to expected value of their distribution.…
Acquired resistance is one of the major barriers to successful cancer therapy. The development of resistance is commonly attributed to genetic heterogeneity. However, heterogeneity of drug penetration of the tumor microenvironment both on…
Prognostic genes have been well studied within each type of cancer. However, investigations of the similarities and differences across cancer types are rare. In view of the optimal course of treatment, the classification of cancers into…
We consider a stochastic model of transcription factor (TF)-regulated gene expression. The model describes two genes: Gene A and Gene B which synthesize the TFs and the target gene proteins respectively. We show through analytic…
Control theory has seen recently impactful applications in network science, especially in connections with applications in network medicine. A key topic of research is that of finding minimal external interventions that offer control over…
The widespread presence of antibiotic resistance and virulence among Staphylococcus isolates has been attributed to lateral genetic transfer (LGT) between different strains or species. However, there has been very little study of the extent…
While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain…
Pathogens usually exist in heterogeneous variants, like subtypes and strains. Quantifying treatment effects on the different variants is important for guiding prevention policies and treatment development. Here we ground analyses of…
Genetic studies of human traits have revolutionized our understanding of the variation between individuals, and opened the door for numerous breakthroughs in biology, medicine and other scientific fields. And yet, the ultimate promise of…
Personalizing drug prescriptions in cancer care based on genomic information requires associating genomic markers with treatment effects. This is an unsolved challenge requiring genomic patient data in yet unavailable volumes as well as…
Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic and…
Observed differences in mean phenotypic values across human groups have attracted renewed interest with the rise of large-scale genomic studies and polygenic risk prediction. However, the genetic basis of these differences is far more…
In oncology the efficacy of novel therapeutics often differs across patient subgroups, and these variations are difficult to predict during the initial phases of the drug development process. The relation between the power of randomized…
Successful sequencing experiments require judicious sample selection. However, this selection must often be performed on the basis of limited preliminary data. Predicting the statistical properties of the final sample based on preliminary…