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Array-Related Projects Net $76M in NIH Stimulus Grants for FY 2009

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By Justin Petrone

The National Institutes of Health has awarded more than $76 million in fiscal 2009 funding designed to help support microarray and biochip-based projects, according to an analysis of the NIH funding database conducted by BioArray News.

While the majority of the new financing, made available via the American Recovery and Reinvestment Act of 2009, will support genome-wide association studies and related projects, other segments of the array market, including copy-number variation analysis, gene expression, and bioinformatics, have benefited from the federal stimulus package.

BioArray News identified at least 92 grants worth $76.2 million in FY '09 that intend to use microarray or microfluidic biochip technology by compiling a list of project titles that mention array technology or array-related research areas.

Of those, 92, 28 grants worth more than $42 million combined were awarded to GWAS-related projects; eight grants worth over $11 million combined will support gene-expression profiling; five grants worth a combined $6.7 million will aid researchers in investigating the role of copy number variation; nine projects worth a combined $4 million will support to the development of pathogen-detection platforms; and 12 grants worth a combined $2.5 million will enable the creation of data analysis tools.

It is worth noting that some of the projects funded use a mix of more than one technology and others could fit into a number of categories by looking at, for instance, both gene expression and copy number variation in the same study. For a full breakout of array-related grants by category, see the charts below.

GWAS

Genome-wide association studies and related projects netted the most funding, according to the analysis. The largest award went to support the efforts of the CHARGE Consortium, a group of multiple population-based cohort studies led by Eric Boerwinkle at the University of Texas Health Science Center.

Entitled "Building on GWAS for NHBLI-Disease: the CHARGE Consortium," the $12.3 million project pools the efforts of the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Coronary Artery Risk Developments in Young Adults study to "identify susceptibility genes underlying genome-wide significant and well-replicated GWAS findings for heart, lung and blood diseases and their risk factors," according to the grant abstract.

For all of these studies, DNA samples have already been isolated and phenotype data is available for analysis, the abstract states. The proposed research will take a two-pronged approach to following-up previously conducted GWA studies. First, the consortium will carry out targeted sequencing and replication genotyping in 60 genomic regions influencing 15 phenotypes. Second, the group will conduct whole-genome sequencing of 230 African-American ARIC participants, validated by genotyping in additional samples.

The Fred Hutchinson Cancer Research Center in Seattle received the second highest GWAS-related award. Led by investigator Ulrike Peters, the center will spend $4.6 million to investigate the causes of colorectal cancer. Specifically, the center aims to expand ongoing colorectal cancer GWA studies to encompass an additional 3,811 cases and 3,811 controls. According to the grant's abstract, Peters' team will use Illumina's Human 610-Quad HD BeadChips for the study.

A team led by Gerard Schellenberg at the University of Pennsylvania has received $3.4 million to perform a GWA study of Alzheimer's disease. According to the grant abstract, the project will perform GWA studies using a "high-density genotyping platform to detect small effect loci that contribute to AD susceptibility", "analyze a large familial AD collection using the same genotyping platform so that family-based methods can be applied to AD gene discovery," and "provide a DNA, phenotype, and genotype resource of well- characterized AD cases, mild cognitive impaired subjects, and controls for the genetics community to analyze." The grant abstract did not mention which array platform Schellenberg's team will use in the study.

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The NIH also awarded $2.4 million to a team led by Andrea Dunaiff at Northwestern University to conduct a GWA study of polycystic ovary syndrome phenotypes. According to the grant abstract, Dunaiff's team seeks to identify PCOS susceptibility alleles in around 1,200 PCOS cases and around 3,600 unselected population-based female controls. "Promising variants will be further investigated using replication studies of the 1,536 most promising SNPs in an independent cohort of 1,800 PCOS cases and 5,400 unselected female controls," the abstract states. It does not mention which array platform will be used.

In total, ARRA funds will support GWA studies of about 20 different diseases and conditions, including food allergy, emphysema, osteoporosis, atherosclerosis, endometrial cancer, periodentitis, pancreatitis, bladder cancer, kidney disease, nephropathy, ischemic brain vascular injury, schizophrenia, and craniofacial microsemia.

Not all GWAS-related funds will directly support studies, though. Some projects have been funded to provide logistical support to researchers involved in GWA studies or to examine better ways of performing such efforts.

A team led by Edwin Van Den Oord at Virginia Commonwealth University, for example, was awarded nearly $148,000 to "develop a flexible framework for designing cost-effective GWAS and optimize subsequent replication efforts," according to the grant's abstract. A group led by Bruce Weir at the University of Washington's department of biostatistics received $110,000 to set up a GWAS coordinating center to "provide the necessary organizational and statistical expertise for integration of data, development of methodologies and tools for both data harmonization and analyses, and for the administration of those tasks needed for a large multi-site scientific study."

Expression

The Allen Institute for Brain Science received the largest gene expression-related stimulus grant. The NIH awarded a team led by Bruce Fischl $8.3 million to build a transcriptional atlas of human brain development.

According to the grant's abstract, the institute aims to create a "multimodal transcriptional atlas of the pre- and postnatal developing human brain." Working with partners at Harvard University, the University of California at Los Angeles, and Yale University, the institute will oversee the creation of a public access web-based portal for viewing, searching and mining of spatiotemporal gene-expression patterns in the anatomical context of human brain development.

The Allen Institute will "create an atlas framework, consisting of a set of de novo multimodal imaging and histological reference atlases spanning human brain development, and a complete informatics structure for mapping, integrating, and presenting transcriptional data in the context of neuroanatomical structure and key developmental events," according to the abstract.

Contributing laboratories will also generate transcriptional data using microarray analysis across the entire fetal brain, RNA-seq second-generation sequencing data to provide "comprehensive genomic coverage in targeted cortical and subcortical structures across 12 developmental stages," and cellular resolution data to "validate and extend the profiling data and to aid interpretation of dynamic spatiotemporal gene expression patterns."

All of the data will be integrated through the centralized web portal, and linked to a series of similar data resources allowing direct comparative analysis between human, non-human primate and rodent model systems, according to the grant abstract. Ultimately, the institute aims to create a "long-lasting resource for the scientific and medical research communities for relating specific transcriptional programs to processes of human brain development."

Other expression projects funded by the NIH include efforts to study schizophrenia, asthma, cancer progression, and immunity.

CNV and SNP studies

The third largest category of projects to receive stimulus grants concerns projects that aim to conduct CNV and SNP analyses. The largest of these projects is being led by Mark Daly at the Broad Institute, which received $4.8 million to support joint SNP and CNV calling in sequence data from the 1000 Genomes Project.

According to the grant abstract, the project has a number of goals. The first is to convert raw intensity data from the platforms used in the 1000 Genomes Project into "accurate four-base probabilities, refining and calibrating the underlying base-call probabilities, and increasing accuracy." Another goal is to "develop and implement an integrated approach to SNP and CNV detection" that uses these probabilities and "combines information across multiple samples, and exploits existing information from genotyping arrays, increasing sensitivity and accuracy for both SNPs and structural variants." Finally, the project aims to develop "user-friendly software for browsing and applying 1000 Genomes Project data in disease research, making project data on sequence variation and linkage disequilibrium accessible and easily usable to the wider genetics community."

A number of other CNV and SNP-related projects received stimulus funds. Charles Lee at Brigham and Women's Hospital in Boston received more than $542,000 to investigate copy number variation in the genome. Tamim Shaikh of the Children's Hospital of Philadelphia received $271,000 to study copy number alterations in genomic disorders. Both Lee and Shaikh are involved in the development of databases of human genomic variation (see BAN 9/1/2009, BAN 7/172009).

According to Lee's grant, he will use the funding to use "state-of-the-art, cross-platform genomic technologies to better characterize the extent and frequency of [copy number variation] and its potential to cause or influence susceptibility to disease."

The goal of Shaikh's proposal is to identify "previously undetectable, disease-causing" copy number alterations in patients with multiple congenital abnormalities. "The identification of genomic regions altered in MCA patients will allow a better understanding of the mechanisms underlying this group of disorders," according to the abstract. CHOP can then begin to "assess the role of genes in these regions that may be critical to early human developmental pathways."



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