Biology subjects

Wildman, D. E.

Publications and source records attributed to Wildman, D. E..

4 recordsLinked to original sources

bioRxiv2018

Computational performance and accuracy of Sentieon DNASeq variant calling workflow

As reliable, efficient genome sequencing becomes more ubiquitous, the need for similarly reliable and efficient variant calling becomes increasingly important. The Genome Analysis Toolkit (GATK), maintained by the Broad Institute, is currently the widely accepted standard for variant calling software. However, alternative solutions may provide faster variant calling without sacrificing accuracy. One such alternative is Sentieon DNASeq, a toolkit analogous to GATK but built on a highly optimized backend. We evaluated the DNASeq single-sample variant calling pipeline in comparison to that of GATK. Our results confirm the near-identical accuracy of the two software packages, showcase perfect scalability and great speed from Sentieon, and describe computational performance considerations for the deployment of Sentieon DNASeq.

bioinformatics↗

bioRxiv2018

DNA Methylation Explains a Subset of Placental Gene Expression Differences Based on Ancestry and Altitude

AbstractObjectives: The most pronounced effect of high altitude (>2700m) on reproductive outcomes is reduced birth weight. Indigenous Bolivians (Andean Native Americans) residing for generations at high altitudes have higher birth weights relative to more recent migrants of primarily European ancestry. Previous research demonstrated that the placenta is a key contributor to the preservation of Andean birth weight at high altitude. Our current research investigated how gene expression and epigenetics contributes to the conservation of birth weight at high altitude by examining mRNA expression and DNA methylation differences between placentas of Andeans and those of European ancestry residing at high and low altitude.\n\nMethods: Genome-wide mRNA expression and DNA methylation of villous placenta tissue was quantified utilizing microarray technology. Subjects were of Andean and European ancestry and resident at high (3600m) or low (400m) altitudes. Differentially expressed genes (DEGs) associated with altitude or ancestry were identified (FDR<0.1, |fold change|>1.25). To predict which DEGs could be regulated by methylation we tested for correlation between gene expression and methylation values.\n\nResults: 69 DEGs associated with altitude (n=36) or ancestry (n=34) were identified. Altitude-associated DEGs included members of the AP-1 transcription factor family. Ancestry-associated DEGs were implicated in inflammatory pathways and associated with pro-angiogenic macrophages. More ancestry-associated DEGs correlated significantly (n=17) (FDR<0.1) with promoter or gene body methylation (p=0.0242) when compared to altitude associated DEGs (n=8).\n\nConclusions: Compared to altitude-associated DEGs, methylation regulates more ancestry-associated DEGs, potentially allowing for rapid modification in the expression of inflammatory genes to attract pro-angiogenic macrophages as a means of promoting placental capillary growth in Andeans, regardless of altitude.

genomics↗

bioRxiv2018

Performance benchmarking of GATK3.8 and GATK4

Use of the Genome Analysis Toolkit (GATK) continues to be the standard practice in genomic variant calling in both research and the clinic. Recently the toolkit has been rapidly evolving. Significant computational performance improvements have been introduced in GATK3.8 through collaboration with Intel in 2017. The first release of GATK4 in early 2018 revealed significant rewrites in the code base, as the stepping stone toward a Spark implementation. As the software continues to be a moving target for optimal deployment in highly productive environments, we present a detailed analysis of these improvements, to help the community stay abreast with changes in performance. We re-evaluated the options previously identified as advantageous, such as threading, parallel garbage collection, I/O options and data-level parallelization. Based on our results, we consider the performance and cost trade-offs of using GATK3.8 and GATK4 for different types of analyses.

bioinformatics↗

bioRxiv2017

The Core Transcriptome Of Mammalian Placentas And The Divergence Of Expression With Placental Shape

IntroductionThe placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved.\n\nMethodUsing RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades.\n\nResultsWe identified a set of 115 core genes which is expressed (FPKM[≥] 10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1). We also identified multiple pre-eclampsia associated genes which are differentially expressed in Homo sapiens when compared to the other 13 species. Multiple genes are significantly associated with placenta morphology, including EREG and WNT5A which are both associated with placental shape.\n\nDiscussion115 genes are important for the core functions of the placenta in all eutherian species analyzed. The molecular functions and pathways enriched in the core placenta align with the evolutionarily conserved functionality of the placenta.

genomics↗