Interpretation Of Genomic Information Research Articles

Impute.me: An Open-Source, Non-profit Tool for Using Data From Direct-to-Consumer Genetic Testing to Calculate and Interpret Polygenic Risk Scores.

To date, interpretation of genomic information has focused on single variants conferring disease risk, but most disorders of major public concern have a polygenic architecture. Polygenic risk scores (PRSs) give a single measure of disease liability by summarizing disease risk across hundreds of thousands of genetic variants. They can be calculated in any genome-wide genotype data-source, using a prediction model based on genome-wide summary statistics from external studies. As genome-wide association studies increase in power, the predictive ability for disease risk will also increase. Although PRSs are unlikely ever to be fully diagnostic, they may give valuable medical information for risk stratification, prognosis, or treatment response prediction. Public engagement is therefore becoming important on the potential use and acceptability of PRSs. However, the current public perception of genetics is that it provides “yes/no” answers about the presence/absence of a condition, or the potential for developing a condition, which in not the case for common, complex disorders with polygenic architecture. Meanwhile, unregulated third-party applications are being developed to satisfy consumer demand for information on the impact of lower-risk variants on common diseases that are highly polygenic. Often, applications report results from single-nucleotide polymorphisms (SNPs) and disregard effect size, which is highly inappropriate for common, complex disorders where everybody carries risk variants. Tools are therefore needed to communicate our understanding of genetic vulnerability as a continuous trait, where a genetic liability confers risk for disease. Impute.me is one such tool, whose focus is on education and information on common, complex disorders with polygenetic architecture. Its research-focused open-source website allows users to upload consumer genetics data to obtain PRSs, with results reported on a population-level normal distribution. Diseases can only be browsed by International Classification of Diseases, 10th Revision (ICD-10) chapter–location or alphabetically, thus prompting the user to consider genetic risk scores in a medical context of relevance to the individual. Here, we present an overview of the implementation of the impute.me site, along with analysis of typical usage patterns, which may advance public perception of genomic risk and precision medicine.

Genetics and Genomics of Breast Cancer: update and translational perspectives.

In the recent years the rapid scientific innovation in the evaluation of the individual's genome have allowed the identification of variants associated with the onset, treatment and prognosis of various pathologies including cancer, and with a potential impact in the assessment of therapy responses. Despite the analysis and interpretation of genomic information is considered incomplete, in many cases the identification of specific genomic profile has allowed the stratification of subgroups of patients characterized by a better response to drug therapies. Individual genome analysis has changed profoundly the diagnostic and therapeutic approach of breast cancer in the last 15 years by identifying selective molecular lesions that drive the development of neoplasms, showing that each tumor has its own genomic signature, with some specific features and some features common to several sub-types. Several personalized therapies have been (and still are being) developed showing a remarkable efficacy in the treatment of breast cancer.

Deliberations of a precision medicine tumor board.

e13005Background: While precision medicine shows increasing promise in oncology, substantial uncertainty surrounds the interpretation of genomic information and assigning clinical value. We examine...

Prenatal diagnostic conundrum involving a novel ATP7A duplication

Prenatal diagnostic conundrum involving a novel <i><scp>ATP7A</scp></i> duplication

ISPOT: a web tool for the analysis and recognition of protein domain specificity

Methods that aim at predicting interaction partners are very likely to play an important role in the interpretation of genomic information. iSPOT (iSpecificity Prediction Of Target) is a web tool (accessible at http://cbm.bio.uniroma2.it/iSPOT) developed for the prediction of protein-protein interaction mediated by families of peptide recognition modules. iSPOT accesses a database of position specific residue-residue interaction frequencies for members of the SH3 and PDZ protein domain families. The software utilises this database to provide a score for any potential domain peptide interaction. iSPOT: 1. evaluates the likelihood of the interaction between any of the peptides contained in an input protein and a list of domains of the two different families; 2. searches in the SWISS-PROT database for potential partners of a query domain; and 3. has access to a repository of all the domain/target peptide interaction data.