Making sense of mutations

Collaboration seeks to understand genetic changes iPSCs acquire during differentiation

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SAN FRANCISCO—Real Time Genomics Inc. (RTG), a genomeanalytics company, and the J. Craig Venter Institute (JCVI), a not-for-profitgenomic research institute, have established a long-term strategiccollaboration to understand and analyze the genetic changes that inducedpluripotent stem cells (iPSCs) may acquire during the process ofdifferentiation. 
RTG and JCVI also announced a collaboration to discover andvalidate highly accurate human variant information using the Venter humanreference diploid genome and associated orthogonal information.
The teams will deposit this information into the publicdatabases for use by the life- science community. The two organizations hope todefine best practices and to create standardized reference datasets for thegenome sequencing community.
RTG, which offers software tools and applications for theextraction of unique value from genomes, applies the combination of itspatented core technology and computational expertise in algorithms to solveproblems in next-generation genomic analysis. JCVI, a world leader in genomicresearch, was formed in October 2006 through the merger of several affiliatedand legacy organizations: The Institute for Genomic Research and the Center forthe Advancement of Genomics, the J. Craig Venter Science Foundation, the JointTechnology Center and the Institute for Biological Energy Alternatives.
According to Mark Adams, scientific director of JCVI, thereis considerable interest in understanding the nature of de-novo mutations that are acquired during reprogramming anddifferentiation of iPSCs. While these mutations might affect how iPSCs behaveas disease models and could limit the therapeutic use of these cells, there are"many pitfalls in analyzing sequence data to locate and interpret these raremutations."
Adams adds, "Since sequencing and publishing the Venterreference human genome in 2007, we have built a significant dataset around thisgenome and want to help others leverage the information to improve their ownresearch."
JVI has "worked with Francisco De la Vega of RTG for sometime on analysis of the HuRef genome sequence," according to Adams. He saysHuRef is "unique among human genome assemblies for having extensive data frommultiple sequencing platforms including Sanger, Illumina, SOLiD and CGI. Thehigh-quality genome and now phased haplotypes from Ewen Kirkness's recent paper( make it by far the bestcharacterized human genome." Adams describeds it as "an excellent reference forevaluating the quality of new sequencing approaches and analysis methods" andsays RTG plans to continue to improve the HuRef sequence and demonstrate itsvalue as a reference standard for comparing analytical methods.
"This should also highlight the power of RTG's software," henotes.
According to Adams, JCVI will also work with RTG on analysisof data from a series of cell lines derived from the HuRef individual by iPScell reprogramming. 
"The accuracy of the HuRef sequencing means that discerningnovel SNVs acquired during reprogramming and differentiation is enhanced," heexplains. "RTG has new methods of joint SNV detection across related samplesand is an ideal partner for these projects because of the ability to rapidlyanalyze data from multiple sequencing platforms with improved accuracy of theresulting variant catalog."
As part of the collaboration, JCVI will be using the RTGplatform and working directly with RTG scientists to identify SNPs, indels,structural variants and de-novomutations in data from both projects. The RTG platform will be seamlesslyintegrated into JCVI's existing pipeline infrastructure.
De La Vega, who is vice president of genome sciences at RTG,describes the stem cell collaboration with JCVI as "an exciting opportunity tomove our technology into new areas as cell lineage progression studies arebecoming important in a wide range of NGS applications." He says that a problemin clinical applications of sequencing is "the difficulty knowing whethersequencing data and results meet specific accuracy criteria."
De La Vega adds, "RTG and the broader community are workingto collectively settle on a set of validated datasets to improve research.Because JCVI has considerable orthogonal information related to the Venterreference genome, including Sanger long-read sequence data, data from multiplenext-generation sequencing platforms, and even RNAseq data and full phasinginformation, there is an opportunity to contribute a standard back to thecommunity to improve the sensitivity and specificity of human diseaseapplications using NGS.
"We hope that these interactions will be completed in thenext several months and lead to further interactions with RTG," Adamsconcludes.

Real Time Genomics and Knome team up to speed genomeanalysis
SAN FRANCISCO—Real Time Genomics Inc. (RTG) also announcedlast month that it will work with Knome Inc. to integrate the RTG Variantplatform into every shipment of the knoSYS100 interpretation system. Theagreement enables customers to easily purchase the RTG analytics engine as anupgrade to the system. 
According to the companies, the product will combine twoworld-class commercial platforms to deliver end-to-end genome analytics andinterpretation with superior accuracy and speed. Financial terms of theagreement were not disclosed.
"In the past year, demand for genome interpretation hassurged as translational researchers and clinicians adopt sequencing for humandisease discovery and diagnosis," said Wolfgang Daum, CEO of Knome, in astatement. "Concomitant with that demand is the need for accurate andeasy-to-use industrial grade analysis that meets expectations of clinical accuracy.The RTG platform is both incredibly fast and truly differentiating to customersdoing family studies, and we are excited to add such a powerful platform to theknoSYS ecosystem."
The partnership simplifies the purchasing process byallowing knoSYS customers to purchase the RTG platform directly from Knomesales representatives.
"The Knome system is a perfect complementary channel tofurther expand our commercial effort to bring the RTG platform to market," saysSteve Lombardi, CEO of RTG. "Knome has built a recognizable brand around humanclinical genome interpretation, and by delivering the RTG platform within theirsystem, both companies are simplifying genomics to help customers understandhuman disease and guide clinical actions."

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