ABRF 2013
BIOFORMATICS Management System designed specifically for AP-MS inter-
4
Quantitative Multifactor Dimensionality Reduction
Method for Detecting Gene-Gene Interaction
Jiang Gui, Diane Gilbert-Diamond, Peter Andrews,
Jason H. Moore
Geisel School of Medicine, Dartmouth College
Background and Objective: The problem of identifying
SNP-SNP interactions in case-control studies has been studied
extensively and a number of new techniques have been devel-
oped. Little progress has been made, however in the analysis of
SNP-SNP interactions in relation to continuous data. Meth-
ods: We present an extension of the two class multifactor
dimensionality reduction (MDR) algorithm that enables detec-
tion and characterization of epistatic SNP-SNP interactions in
the context of Quantitative trait. The proposed Quantitative
MDR (Quant-MDR) method handles continuous data by
modifying MDR’s constructive induction algorithm to use T
Test. Results: We then applied Quant-MDR to genetic data
from the ongoing prospective Prevention of Renal and Vascular
End-Stage Disease (PREVEND) study. We identified that
BR2_58CT&ATR1AC is the top SNP-SNP interaction that
assciated with Tissue plasminogen activator (tPA) level for male
and ACEID&BRB2EX1 is the top interaction for female tPA
expression. Discussion and Conclusions: Quant-MDR is capa-
ble of detecting interaction models with weak main effects.
These epistatic models tend to be dropped by traditional linear
regression approaches. With improved efficiency to handle
genome wide datasets, Quant-MDR will play an important
role in a research strategy that embraces the complexity of the
genotype-phenotype mapping relationship.
5 Data Highlights Mechanisms of Ewing Sarcoma
Keeping Track of Interactomes Using the ProHits
LIMS
Anne-Claude Gingras1,2, Guomin Liu1, Jianping Zhang1,
Hyungwon Choi3, Brian Raught4, Alexey I. Nesvizhskii5,
Mike Tyers6
1
Samuel Lunenfeld Research Institute, Mt Sinai Hospital,
Toronto, ON, Canada, 2Department of Molecular Genetics,
University of Toronto, 3Saw Swee Hock School of Public
Health, National University of Singapore, Singapore,
4
Ontario Cancer Institute and Department of Medical
Biophysics, University of Toronto, Toronto, Ontario,
Canada, 5Department of Pathology and Center for
Computational Medicine and Bioinformatics, University of
Michigan, Ann Arbor, 6Institute for Research in Immunology
and Cancer, Université de Montréal, Montréal, Québec,
Canada
Affinity purification coupled with mass spectrometry
(AP-MS) is a robust technique used to identify protein-
protein interactions. With recent improvements in sample
preparation, and dramatic advances in MS instrumentation
speed and sensitivity, this technique is becoming more
widely used throughout the scientific community. To meet
the needs of research groups both large and small, we have
developed software solutions for tracking, scoring and ana-
lyzing AP-MS data. Here, we provide details for the instal-
lation and utilization of ProHits, a Laboratory Information
JOURNAL OF BIOMOLECULAR TECHNIQUES, VOLUME 24, SUPPLEMENT, MAY 2013
POSTER ABSTRACTS
action proteomics that we distribute freely to the scientific
community at ProHitsMS.com, and which is under contin-
uous development. The complete ProHits solution1 per-
forms scheduled backup of mass spectrometry data and
initiates database searches (Mascot, X!Tandem, COMET,
SEQUEST and the output from the TransProteomics Pipe-
line are now supported). It stores search results and enables
linking the mass spectrometry data to entries in the rela-
tional database module called “Analyst”, which is also avail-
able as a stand-alone application (including as an easy-to-
install virtual machine implementation2). ProHits Analyst is
organized in a hierarchical manner by project, bait, experi-
ment and sample and also serves as an electronic notebook.
When a sample is created, mass spectrometry search results
can be uploaded. Search results can be explored using a series
of viewers, filtered based on mass spectrometry quality,
frequency of detection or background lists, viewed in Cyto-
scape-Web or exported to text or as a PSI XML format for
deposition in interaction databases. Importantly, however,
search results can be further analyzed using the SAINT
statistical tool which is seamlessly integrated within ProHits
to derive interaction confidence scores(3-5). With the inte-
gration with a number of open source tools and public
repositories, ProHits facilitates transparent analysis and re-
porting of AP-MS data.
1
PMID:20944583
2
PMID:22948730
3
PMID:20489023
4
PMID:21131968
5
PMID:22948729
6
Isoform-level Analysis of Next Generation Sequence
Progression
Winston Brasor, Jean-Noel Billaud, Carla Bullitt
Ingenuity Systems
Ewing Sarcoma (ES) is a prototypical translocation sar-
coma, which harbors characteristic translocations fusing the
5⬘ portion of the EWS gene with the 3⬘ region encoding the
DNA binding domain of one of five ETS family genes. ES
behaves as an aberrant reprogramming of mesenchymal
stem cells and is the second most frequent bone tumor in
adolescents and young adults. To understand the molecular
mechanisms of tumorigenesis and metastatic processes in
ES, gene expression profiling ES patient samples was per-
formed using NGS technology. In this study we present the
results of using Ingenuity威 iReport™, a software applica-
tion employing bioinformatics and biological interpretation
best practices, to demonstrate the differences between met-
astatic and primary tumor samples from one representative
patient with ES. Analysis in iReport highlights the unique
value of RNA-Seq (compared to traditional gene expression
microarrays) by providing functional information on tran-
script isoforms produced in metastatic tumors (relative to
primary), and generating testable hypotheses as to the mech-
anisms of ES progression. We characterized and identified
signalling and metabolic pathways (such as Glucose and
Fatty Acid Metabolism) and biological processes (such as
Cellular Invasion) that may be involved in the progression of
S31