Genome Analysis - September 2012

Featured NGS Project:
Pediatric Cardiac Genetics Consortium (PCGC)

As next generation sequencing platforms and whole genome methods are more ubiquitously adopted across individual academic research institutes, there are increased opportunities to conduct disease-specific, multi-center studies using this technology. CBMi is interested in defining the technological and governance challenges associated with the massive amount of potentially identifiable data, and in characterizing the ethical issues of data sharing in a multi-center genomics initiative.

The Pediatric Cardiac Genetics Consortium, a component of the NHLBI’s signature Bench to Bassinet program, aims to identify the genetic causes of human congenital heart disease and to relate genetic variants present in the congenital heart disease patient population to clinical outcomes. The PCGC recently awarded CBMi with a 5-year, $3.5M award to serve as the Informatics Hub for various genomic data platforms, including next generation sequencing, for nine participating performance sites, including Harvard, Columbia, Mount Sinai, CHOP, and Yale.

In its role, CBMi is:

Receiving and analyzing genomic and clinical data from over 4,000 patients with congenital heart defects, comprising over 14 Terabytes of information to date.
Developing web-based data interfaces to allow researchers to query and explore genomic findings in the context of a patient’s disease and clinical outcomes data.
Working with the various stakeholders within each of the sites to determine clinical and genomic data standards and governance necessary for a working centralized database.
Providing an interface that controls all inputs and outputs necessary for the submission and transfer of data.
Providing a mechanism for the efficient transfer of annotated data sets from each site.
Developing an analysis framework that allows users to upload sequence data and download results.
Developing a querying and reporting tool that will allow consortium members the ability to learn more about how cardiac disease is associated with genomic assays.

Focus: Mitomaster Relaunched

Inherited mutations in the DNA of mitochondria, the body's "cellular power plants", are responsible for a surprisingly wide variety of disorders that affect children and adults. Despite its small size (16kbp), the mitochondrial genome, which is independent of the cell's nuclear DNA, is the host to thousands of known mutations. For researchers and clinicians, identifying mitochondrial mutations potentially inherited illnesses is critical to making a correct diagnosis. As part of their research into mitochondrial diseases, CHOP researcher Doug Wallace and his associates have been collecting and curating mitochondrial mutations for almost two decades in their MITOMAP database.

The ability to screen newly sequenced mitochondrial genomes from patients will become increasingly important as molecular diagnostics becomes standard practice. Mitomaster is a web application that allows users to submit clinical mitochondrial sequences to find mutations - known and novel. Mitomaster calculates the predicted coding effect of mutations and performs lookups against the MITOMAP database. The tool also allows users to identify the "haplogroup" or ancestry of submitted mitochondrial sequences.

Under the guidance of the Wallace Lab at CHOP's Center for Mitochondrial and Epigenomic Medicine, developers in the CBMi Bioinformatics Core have updated and relaunched the Mitomaster tool to add new functionality and a new user interface. Dr. Douglas Wallace presented Mitomaster at the Paris UNESCO conference June 11, 2012.

Meet the Team
Patrick Warren
Director of Genomic Medicine

Patrick Warren, PhD Patrick joined CBMi in April of 2012 as the Director of Genomic Medicine. He directs the Genome Analysis group and works with researchers, clinicians, regulatory groups and informaticians to incorporate genome-based discoveries into the electronic health record through clinically governed decision support systems. Before joining CBMi, Patrick served as Executive Director of Global Informatics Systems at the Novartis Institute of Biomedical Research (NIBR) and as Director of Bioinformatics at GlaxoSmithKline (GSK). At NIBR, he and his team of analysts and programmers developed numerous applications, data management systems, and analytical frameworks for the support of general workflows for target discovery, screening, lead optimization, candidate selection, preclinical development, and clinical studies.

He also led efforts to create a unified enterprise view of data through an integrated, high performance information management system that included data entry, capture, aggregation and access. At GSK, Patrick supervised the creation of systems that integrate data from genomic, and other “–omic” platforms to support systems biology efforts in oncology and toxicology. He completed a post doctoral fellowship in Molecular Biology at E.I. DuPont’s Central Research Station, received his PhD in Biochemistry from University of Nebraska and his bachelors degree in Chemistry from Southern Oregon University.

Publications

Recent publications by members of the Genomic Analysis team include:

NMNAT1 mutations cause Leber congenital amaurosis
Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA.
Source
1] Department of Pediatrics, Division of Human Genetics, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. [2] Department of Pediatrics, Division of Child Development and Metabolic Disease, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. [3]

DNA Methylation is Associated with Altered Gene Expression in AMD.
Hunter A, Spechler P, Cwanger A, Song Y, Zhang Z, Ying GS, Hunter AK, Dezoeten E, Dunaief J. DNA Methylation is Associated with Altered Gene Expression in AMD. Invest Ophthalmol Vis Sci. 2012 Mar 12. PMID: 22410570

Potential of human umbilical cord blood mesenchymal stem cells to heal damaged corneal endothelium.
Joyce NC, Harris DL, Markov V, Zhang Z, Saitta B. Mol Vis. 2012;18:547-64. Epub 2012 Mar 2.

Characterization of DNA methylation and its association with other biological systems in lymphoblastoid cell lines.
Zhang Z, Liu J, Kaur M, Krantz ID. Genomics. 2012 Apr;99(4):209-19. Epub 2012 Jan 15 PMID: 22269447

About this Newsletter
Genome Analysis(Vol. 2.1. Sept. 2012) provides the latest news in next generation sequencing (NGS) and bioinformatics from the Center for Biomedical Informatics(CBMi) at The Children's Hospital of Philadelphia.
To subscribe, email chopcbmi@email.chop.edu.

Save the Date
March 26, 2013

The 4th Annual Next Generation Sequencing Symposium will be held on Tuesday March 26, 2013. Mark your calendars for this opportunity to hear about the latest developments in the field and share your experiences with colleagues in an open forum. More information will be provided in early 2013.

Genome Wowser v2.0 Released

Announcing the release of Genome Wowser v2.0, now available in the iTunes store!

Version 2 supports ALL genomes available at UCSC, including:

All builds of the human genome
Mouse
Rat
Chimpanzee
Gorilla
Zebrafish
Pufferfish (2 species)
Fruitfly (11 species)
C. elegans
Yeast
...and 40 more species

Other new features include:

Users can define custom UCSC mirror sites
Customizable track parameters
Session IDs are exposed for portability to web browsers.
iOS 6 support added

Download Genome Wowser.

CBMi Collaborates with CHOP Molecular Genetics Lab

Noonan Test Available

The Molecular Genetics Laboratory at the Children’s Hospital of Philadelphia announced the introduction of a diagnostic test for the Noonan Spectrum of disorders using next generation sequencing technology. Sequencing for the Noonan spectrum panel will be performed on Illumina’s MiSeq in combination with Raindance capture technology.

Avni Santani, Scientific Director of the Molecular Genetics Laboratory, and the team lead for this project, said the laboratory was in a unique position to harness the power of next generation sequencing and translate in to a clinical diagnostic test. “Successful adoption of next generation sequencing (NGS) technology for diagnostic testing requires coordination between the diagnostic laboratory, informaticists, clinicians and regulatory agencies. This project which was collaboration between the Molecular Genetics Laboratory team, the Center for Applied Genomics and Center for Biomedical Informatics was focused on establishing a rigorous clinical diagnostic workflow that would be in compliance with CAP regulatory standards.

Targeted resequencing still provides the most cost effective approach for high quality diagnostic testing of heterogeneous genetic disorders in a rapid and efficient manner, according to Dr. Santani. The Molecular Genetics Laboratory at CHOP is currently validating additional disease panels on different capture methods including Agilent’s Sureselect and Life Technologies’ Ampliseq.
Contact Dr. Santani for more information.
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Meet with our experts

Members from our team are available to meet with you every Tuesday and Thursday in Abramson Research Center Room 710B. Learn about our capabilities and how we can support your research here at CHOP

Contact

For consultations,
please contact Patrick Warren.

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