Here, we provide a web-based application, Cancer-Related Analysis of Variants Toolkit, designed with an easy-to-use interface to facilitate the high-throughput assessment and prioritization of genes and missense alterations important for cancer tumorigenesis.
As we move to implement changes, regulatory agencies and industry are beginning to adopt tiered approaches, which leverage high-throughput screening technologies for prioritization and read across, followed by interrogation of "hit chemicals" with more rigorous dose-response assessment either in fit-for-purpose human cell-based assays or with traditional in vivo tests.
To date, high-throughput screening for chemical prioritization has been largely limited to small numbers of genetic variants, and to models that are limited in diversity.
Coupled with development of decision frameworks (e.g., Combes et al. 2003), data from these high-throughput screens may facilitate prioritization of any further testing in vivo, for example, as for substances identified as potentially hazardous under the European regulation on Registration, Evaluation, Authorisation, and Restriction of Chemical Substances (REACH) (European Commission 2006).
A recent review [ 22] contrasts '-ology' strategies that typically test a priori hypotheses with '-omics' strategies that adopt more agnostic, exploratory approaches, stressing that "... discovery-based approaches do not eschew hypotheses; rather, they seek to elevate hypothesis testing to a new level, by allowing high-throughput hypothesis generation and prioritization" [ 22].
Because the candidate PID gene list is still large, this approach of integrating data from high-throughput studies would allow further prioritization of genes for confirmation in patients with PID where the exact gene is not yet identified.
Wambaugh, JF; Setzer, RW; Reif, DM; Gangwal, S; Mitchell-Blackwood, J; Arnot, JA; Joliet, O; Frame, A; Rabinowitz, J; Knudsen, TB; Judson, RS; Egeghy, P; Vallero, D; Cohen Hubal, EA, High-throughput models for exposure-based chemical prioritization in the ExpoCast project., Environmental Science & Technology, vol 47 no.
The EPA, through its ToxCast™ program, is already exploring how high-throughput systems can be used for prioritization, as is the NTP, in accordance with its own research program for the twenty-first century the NTP Roadmap that was introduced in 2004.
This methodology could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.
Hindra et al. Strain prioritization for natural product discovery by a high-throughput real-time PCR method.
