Scientists at Scripps Health have received a $382,000 grant from the National Human Genome Research Institute that they will use to develop a publicly available version of a variant annotation pipeline marketed by Cypher Genomics, a Scripps spinout formed last year to commercialize the technology.
According to the grant abstract, the funds will be used to extend the Scripps Genome Annotation and Distributed Variant Interpretation Server, or SG-ADVISER, to incorporate additional annotation types; support annotations of model organisms; provide customized annotations; and to provide tools to process, filter, and visualize the annotations.
Specifically, the researchers intend to include more methods of predicting whether variants are functional or not using currently available open source algorithms; and to replace flat files with a more user-friendly way to visualize the data, Ali Torkamani, director of drug discovery at Scripps Translational Science Institute and a Cypher Genomics founder, told BioInform this week.
He said that the free, web-based version of the offering will be available only to academics while commercial users will have to work with Cypher Genomics, which offers commercial annotation services based on the software.
Cypher uses the SG-ADVISER pipeline to provide genomic data interpretation and analysis services for disease risk assessment and forensic purposes. The pipeline includes computational tools to interrogate the molecular effects of sequence variation; and consolidates disease risk and phenotype expression information for individual genomic health profile reporting (BI 12/22/2011).
Last October, the company was tapped to clinically annotate the whole genomes of 1,000 individuals, aged 80 and older, who are participating in the Wellderly study, a research initiative by Scripps that's exploring the genetics behind healthy aging (BI 10/7/2011).
Scripps chose to develop a publicly available version of SG-ADVISER to offer an option for cash-strapped academic institutions who can't afford the cost of Cypher's services, Torkamani said.
"It's not going to have all the nice tools that will be developed by Cypher Genomics to process the data and do rare variant analysis," he said. "It's the basic pipeline."
Like the commercial service, the free offering will offer users four "levels" of annotations, Torkamani said.
First, it annotates all the genomic elements in the region in which the variant is located. For example, it will identify nearby genes or whether the mutation impacts a coding region, splice site, or transcription factor binding site, he said.
Next, he explained, the tool predicts the functional impact of the variant on these genomic elements, such as whether an amino acid change impairs a particular protein's function. It then adds in prior clinical knowledge about the variant such as whether it has been shown to be involved in disease.
Finally, to provide a broader context that encompasses the activities in which a mutated gene is involved, SG-ADVISER adds in systems-level annotations, including information on biological pathways and processes, to identify connections between variants across genes, he said.
Nevertheless, "annotations will only get you so far," Torkamani said. Those who choose to take advantage of Cypher's offering will have access to additional features, such as the ability to do rare variant analysis, prioritize disease-causing mutations in family-based studies, or carry out investigations into idiopathic diseases, he said.
Additionally, Cypher purchases licenses to commercial knowledgebases and uses this information to provide more detailed annotations for customers — a feature not available to researchers who take advantage of the free platform, he said.
The Scripps team expects to have the first iteration of the free web server ready for use by the end of this year, he said.
Other efforts within the bioinformatics community to identify and annotate disease-causing variants in humans include research groups at the Medical College of Wisconsin and the University of Toronto who are developing software systems for that purpose.
MCW's CarpeNovo is currently being used internally to identify rare mutations in clinical cases and in research efforts in cardiovascular disease, eye disease, cancer, and developmental and multisystem disorders, though its developers are considering making it publicly available.
UT's MedSavant, on the other hand, which is currently being used in an autism sequencing project, is available for general use although it use is restricted to research annotations at present (BI 11/18/2011).
Meanwhile, Cypher Genomics competes with companies like Omicia, which also offers annotation tools for genomic data, and Personalis, which focuses on the medical interpretation of human genomes for research and eventually clinical applications.
A third competitor in the space is Knome, which spun out a new informatics software-as-a-service product called KnomeBase that offers tools and services to annotate, compare, and distill raw sequence data in large whole-genome studies.
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