SpliceCore: A Cloud-Based Software Platform to Translate Alternative Splicing Events into Therapeutic Targets Using RNA-seq Data

Abstract Overmillion people in the US suffer from genetic diseases or cancers caused by mutations of whichdisrupt the regulation of splicingAlternative splicingASerrors have been reported in literature to drivegenetic diseases out ofdescribed to dateIn additiondue to the recent success of FDA approved splicing modulators like Nusinersenalong with fascinating preclinical results underlining the importance of AS as therapeutic targetssplicing research has become of major interest to pharmaceutical companiesEnvisagenics is developing SpliceCoreTMan innovative cloud based software platform using biomedical big data for AS analysis to discover new therapies and biomarkers for complex diseasesOur breakthrough platform combines algorithms and databases developed and experimentally validated at Cold Spring Harbor LaboratoryCSHLSpliceTrapTMfor the detection of splicing activity using RNA seq dataSpliceDuoTMfor the identification of significant splicing variation across biological samplesSpliceImpact TMfor the prioritization of biologically relevant AS variants with therapeutic potentialand TXdbTMa splicing isoform database that connects client s proprietary data to public repositories such as the Cancer Genome AtlasTCGAThanks to the Phase I award SpliceCore was adapted as a cloud based softwareaccelerating scalability and adaptation to the fastevolving market of biomedical Big DataWe now have deployed SpliceCore s back end on three cloud service providersincreased its overall run time by a factor ofdeveloped tools to discover disease specific AS isoformsfinalized and tested a machine learning algorithm to predict the biological impact of ASand experimentally validated some of our new predictions with a success rate ofThe goal for Phase II is to accelerate client acquisition through the development of user interactive applications informed from client s feedback by substantially expanding the platform s knowledgebase and predictive functions with novel AS isoforms extracted frompublic datasetsThusa new version of SpliceCore will be developed to predict regulatory interactions between RNA binding proteins and their RNA targets to assist in the interpretation of aberrant splicing factors through a collaboration with world renowned HHMI Professor DrTom Tuschl from Rockefeller University and developer of NusinersenProfessor DrAdrian Krainer from CSHLEnvisagenics is targeting the global bioinformatics market valued at $billion inwith a CAGR of overSpliceCore could captureof the marketidentify novel drug targetsand design RNA therapeutics from aberrant splicing events prevalent in cancer and a multitude of genetic diseases while increasing the efficiency of Randamp D in biopharma Project Narrative In this SBIR Phase IIEnvisagenics will advance the development of SpliceCoreTMa cloud based software platform for the discovery of drug targets and biomarkers using biomedical big dataTherapeutic screens are increasingly focusing on Alternative SplicingASa biological process that regulates gene product structure and functionStrikinglyof genetic diseases described in literature can be triggered by AS errorsThe recent FDA approval of RNA therapeutic compounds to correct AS errorscombined with increasingly available big datasets and groundbreaking cloud computing provide a unique opportunity for computerized discovery of AS therapeuticsEnvisagenicstechnology will help biomedical researchers to translate basic science into new therapeutic products for cancer and genetic diseasesBy the completion of this projectwe will deploy a user friendlysecured and scalable SpliceCore softwarewith new functionalities ready for integration into biopharmaceutical Research andampDevelopment workflows