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1.  Churchill: an ultra-fast, deterministic, highly scalable and balanced parallelization strategy for the discovery of human genetic variation in clinical and population-scale genomics 
Genome Biology  2015;16(1):6.
While advances in genome sequencing technology make population-scale genomics a possibility, current approaches for analysis of these data rely upon parallelization strategies that have limited scalability, complex implementation and lack reproducibility. Churchill, a balanced regional parallelization strategy, overcomes these challenges, fully automating the multiple steps required to go from raw sequencing reads to variant discovery. Through implementation of novel deterministic parallelization techniques, Churchill allows computationally efficient analysis of a high-depth whole genome sample in less than two hours. The method is highly scalable, enabling full analysis of the 1000 Genomes raw sequence dataset in a week using cloud resources.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0577-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4333267  PMID: 25600152
2.  Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine 
PLoS Pathogens  2014;10(6):e1004209.
Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10−/− mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1− SPI2− or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.
Author Summary
It has long been thought that the nutrient utilization systems of Salmonella would not make effective drug targets because there are simply too many nutrients available to Salmonella in the intestine. Surprisingly, we have discovered that Salmonella relies heavily on a single nutrient during growth in the inflamed intestine, fructose-asparagine (F-Asn). A mutant of Salmonella that cannot obtain F-Asn is severely attenuated, suggesting that F-Asn is the primary nutrient utilized by Salmonella during inflammation. No other organism has been reported to synthesize or utilize this novel biological compound. The novelty of this nutrient and the apparent lack of utilization systems in mammals and most other bacteria suggest that the F-Asn utilization system represents a specific and potent therapeutic target for Salmonella.
PMCID: PMC4072780  PMID: 24967579
3.  Acute physical activity effects on cardiac gene expression 
Experimental physiology  2010;95(11):1071-1080.
Regular bouts of physical activity may cause changes in gene expression that accumulate over time and ultimately affect phenotypes, such as body weight, blood lipid profile, and tumor development. Furthermore, acute activity may affect gene expression and phenotypes differently depending on whether the individual is regularly inactive or active. One-month old male Sprague-Dawley rats (n=72) were equally divided into SED (standard laboratory cage, n=24), PA (large activity box, n=24), and EX (exercise wheel inside standard cage, n=24) groups. At three months of age, half the animals from each group were sacrificed at rest and the other half following 30 minutes of physical activity. RNA was extracted from cardiac tissue, and microarray analysis was performed on 27,000 genes. Select gene results were validated using qPCR. No gene expression differences occurred when comparing all 3-month old groups at rest. A relatively small percentage of genes (1.9%) were differentially expressed (p<0.05) following acute swim activity in all groups but only 37 unique and identifiable genes reached or exceeded two fold differences in expression. The genes Atf3, Fos, Apold1, and Pxdn were expressed differently among SED, PA and EX following acute activity, with a clear separation of the magnitude in gene expression with SED > PA > EX. Differences in gene expression levels in young physically inactive and active animals following acute activity have different regulatory roles in gene networks that affect health-related phenotypes.
PMCID: PMC2956844  PMID: 20696783
acute exercise; gene expression; physical activity
4.  Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays 
BMC Genomics  2007;8:111.
Array-based comparative genomic hybridization (aCGH) is a high-throughput method for measuring genome-wide DNA copy number changes. Current aCGH methods have limited resolution, sensitivity and reproducibility. Microarrays for aCGH are available only for a few organisms and combination of aCGH data with expression data is cumbersome.
We present a novel method of using commercial oligonucleotide expression microarrays for aCGH, enabling DNA copy number measurements and expression profiles to be combined using the same platform. This method yields aCGH data from genomic DNA without complexity reduction at a median resolution of approximately 17,500 base pairs. Due to the well-defined nature of oligonucleotide probes, DNA amplification and deletion can be defined at the level of individual genes and can easily be combined with gene expression data.
A novel method of gene resolution analysis of copy number variation (graCNV) yields high-resolution maps of DNA copy number changes and is applicable to a broad range of organisms for which commercial oligonucleotide expression microarrays are available. Due to the standardization of oligonucleotide microarrays, graCNV results can reliably be compared between laboratories and can easily be combined with gene expression data using the same platform.
PMCID: PMC1868757  PMID: 17470268

Results 1-4 (4)