SpliceCore: A cloud-based platform to detect, quantify and interpret alternative splicing variation from next-generation sequencing data.

DESCRIPTION provided by applicant This Small Business Innovation Research SBIR Phase I project will yield the first prototype of SpliceCore a cloud based resource for the discovery analysis and interpretation of Alternative Splicing AS from RNA seq data of all known diseases are triggered by defects in AS an mRNA maturation process that conveys functional diversity to genes Defective AS is treatable by small molecules and RNA therapeutic compounds some of which are currently in clinical trials SpliceCore will discover new drug targets and biomarkers by extracting disease relevant AS events from RNA seq data The SpliceCore suite combines three algorithms developed and validated at Cold Spring Harbor Laboratory CSHL SpliceTrap for the detection of AS profiles SpliceDuo for the identification of significant AS variation and SpliceImpact for the prioritization of biologically relevant AS events with therapeutic potential We are currently applying these algorithms at CSHL for the discovery of AS events causative of Breast Cancer and to study the role of AS in the mechanism of the Spinal Muscular Atrophy disease The Transcriptomics market was valued at $ billion in and it is expected to reach $ billion by at a CAGR of from to RNA seq data is quickly accumulating in public repositories such as The Cancer Genome Atlas TCGA Geuvadis and the ENCODE project It is expected that the number of pre clinical studies involving AS profiling will increase as a result of the reduced costs of Next Generation Sequencing and the early success of RNA therapeutics SpliceCore will reduce the cost time and complexity associated with AS analysis To deliver a commercial prototype it is necessary to anticipate the demands of multiple users operating simultaneously in a cloud based environment Our objective for this project is to investigate cost effective computing strategies that comply with user tailored specifications Therefore our aims are to develop data processing methods and predictive heuristics that increase computing performance while reducing cloud expenditures to increase detection sensitivity by enabling the discovery of novel AS and use this new capacity to generate a database for cancer specific AS events and Improve SpliceImpact biological interpretation by developing human computer interaction through object recognition and new quantitative metrics that capitalize on andquot omicsandquot datasets There is a great challenge in the market in making cost effective fast and robust data analysis with experimentally testable solutions which Envisagenics innovative technology could relief Envisagenics has a tremendous opportunity due to the increased demand for AS analysis in the biomedical sector reinforced by new high throughput capabilities and promising clinical trials This work is a close collaboration with one of the leading bioinformaticians in the AS field Dr Gunnar R tsch Associate Member at Memorial Sloan Kettering Institute for Cancer Research expert in computational methods for the analysis of big biomedical data and the renown scientists Dr Adrian Krainer Professor at Cold Spring Harbor Laboratory who has deciphered much of the AS mechanism and its implications to Cancer and other genetic disorders PUBLIC HEALTH RELEVANCE At least of all human diseases are triggered by structural changes of the mRNA known as alternative splicing AS The goal of this project is to develop a preliminary cost effective and robust computer program for the analysis of AS using biomedical Big Data This cloud based bioinformatics software will help biomedical researchers worldwide in the development of new therapies and diagnostics Drug target screenings are increasingly focusing on AS motivated by recent success in clinical trials and the introduction of Next Generation Sequencing technologies such as RNA seq Envisagenicsandapos platform will fill the gap between basic science discoveries and therapeutic solutions through comprehensive AS analysis for Cancer and rare genetic diseases By the completion of this project a prototype of SpliceCore will be ready to enter the commercialization phase