Featured NGS Project:
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
Pediatric Cardiac Genetics Consortium (PCGC)
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
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.
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
Focus: Mitomaster Relaunched
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
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
Director of Genomic Medicine
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.
Recent publications by members of the Genomic Analysis team include:
NMNAT1 mutations cause Leber congenital amaurosis
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.
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. 
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,
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 firstname.lastname@example.org.
Save the Date
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
March 26, 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
Pufferfish (2 species)
Fruitfly (11 species)
...and 40 more species
Other new features include:
Download Genome Wowser.
Users can define custom UCSC mirror sites
Customizable track parameters
Session IDs are exposed for portability to web browsers.
- iOS 6 support added
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.
Meet with our experts
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
please contact Patrick Warren.
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The Children's Hospital of Philadelphia | Research Institute.
All rights reserved.