Parallel biocomputing

<p>Abstract</p> <p>Background</p> <p>With the advent of high throughput genomics and high-resolution imaging techniques, there is a growing necessity in biology and medicine for parallel computing, and with the low cost of computing, it is now cost-effective for even small labs or individuals to build their own personal computation cluster.</p> <p>Methods</p> <p>Here we briefly describe how to use commodity hardware to build a low-cost, high-performance compute cluster, and provide an in-depth example and sample code for parallel execution of R jobs using MOSIX, a mature extension of the Linux kernel for parallel computing. A similar process can be used with other cluster platform software.</p> <p>Results</p> <p>As a statistical genetics example, we use our cluster to run a simulated eQTL experiment. Because eQTL is computationally intensive, and is conceptually easy to parallelize, like many statistics/genetics applications, parallel execution with MOSIX gives a linear speedup in analysis time with little additional effort.</p> <p>Conclusions</p> <p>We have used MOSIX to run a wide variety of software programs in parallel with good results. The limitations and benefits of using MOSIX are discussed and compared to other platforms.</p

Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer

<p>Abstract</p> <p>Background</p> <p>Expression quantitative trait loci (eQTL) studies have helped identify the genetic determinants of gene expression. Understanding the potential interacting mechanisms underlying such findings, however, is challenging.</p> <p>Methods</p> <p>We describe a method to identify the <it>trans-</it>acting drivers of multiple gene co-expression, which reflects the action of regulatory molecules. This method-termed <it>co-regulatory expression quantitative trait locus </it>(creQTL) <it>mapping</it>-allows for evaluation of a more focused set of phenotypes within a clear biological context than conventional eQTL mapping.</p> <p>Results</p> <p>Applying this method to a study of endometrial cancer revealed regulatory mechanisms supported by the literature: a creQTL between a locus upstream of STARD13/DLC2 and a group of seven IFNβ-induced genes. This suggests that the Rho-GTPase encoded by STARD13 regulates IFNβ-induced genes and the DNA damage response.</p> <p>Conclusions</p> <p>Because of the importance of IFNβ in cancer, our results suggest that creQTL may provide a finer picture of gene regulation and may reveal additional molecular targets for intervention. An open source R implementation of the method is available at <url>http://sites.google.com/site/kenkompass/</url>.</p

Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension

<p>Abstract</p> <p>Background</p> <p>The nonhuman primate model of glaucomatous optic neuropathy most faithfully reproduces the human disease. We used high-density oligonucleotide arrays to investigate whole genome transcriptional changes occurring at the optic nerve head during primate experimental glaucoma.</p> <p>Results</p> <p>Laser scarification of the trabecular meshwork of cynomolgus macaques produced elevated intraocular pressure that was monitored over time and led to varying degrees of damage in different samples. The macaques were examined clinically before enucleation and the myelinated optic nerves were processed post-mortem to determine the degree of neuronal loss. Global gene expression was examined in dissected optic nerve heads with Affymetrix GeneChip microarrays. We validated a subset of differentially expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched astrocytes from healthy and glaucomatous human donors. These genes have previously defined roles in axonal outgrowth, immune response, cell motility, neuroprotection, and extracellular matrix remodeling.</p> <p>Conclusion</p> <p>Our findings show that glaucoma is associated with increased expression of genes that mediate axonal outgrowth, immune response, cell motility, neuroprotection, and ECM remodeling. These studies also reveal that, as glaucoma progresses, retinal ganglion cell axons may make a regenerative attempt to restore lost nerve cell contact.</p

Highly conserved transcriptional responses to mechanical ventilation of the lung

Cross-species analysis of microarray data has shown improved discriminating power between healthy and diseased states. Computational approaches have proven effective in deciphering the complexity of human disease by identifying upstream regulatory elements and the transcription factors that interact with them. Here we used both methods to identify highly conserved transcriptional responses during mechanical ventilation, an important therapeutic treatment that has injurious side effects. We generated control and ventilated whole lung samples from the premature baboon model of bronchopulmonary dysplasia (BPD), processed them for microarray, and combined them with existing whole lung oligonucleotide microarray data from 85 additional control samples from mouse, rat, and human and 19 additional ventilated samples from mouse and rat. Of the 2,531 orthologs shared by all 114 samples, 60 were modulated by mechanical ventilation [false discovery rate (FDR)-adjusted q value (qFDR) = 0.005, ANOVA]. These included transcripts encoding the transcription factors ATF3 and FOS. Because of compelling known roles for these transcription factors, we used computational methods to predict their targets in the premature baboon model of BPD, which included elastin (ELN), gastrin-releasing polypeptide (GRP), and connective tissue growth factor (CTGF). This approach identified highly conserved transcriptional responses to mechanical ventilation and may facilitate identification of therapeutic targets to reduce the side effects of this valuable treatment