Scholarly Works, Fralin Life Sciences Institute
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Browsing Scholarly Works, Fralin Life Sciences Institute by Department "Electrical and Computer Engineering"
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- COREMIC: a web-tool to search for a niche associated CORE MICrobiomeRodrigues, Richard R.; Rodgers, Nyle C.; Wu, Xiaowei; Williams, Mark A. (PeerJ, 2018-02-15)Microbial diversity on earth is extraordinary, and soils alone harbor thousands of species per, gram of soil. Understanding how this diversity is sorted and selected into habitat niches is a major focus of ecology and biotechnology but remains only vaguely understood. A systems-biology approach was used to mine information from databases to show how it can be used to answer questions related to the core microbiome of habitat-microbe relationships. By making use of the burgeoning growth of information from databases, our tool "COREMIC" meets a great need in the search for understanding niche partitioning and habitat-function relationships. The work is unique, furthermore because it provides a user-friendly statistically robust web-tool (hit p://cot eiruc2.appspot.corn or http://corc-mic.com), developed using Google App Engine, to help in the process of database mining to identify the "core microbiome" associated with a given habitat. A case study is presented using data from 31 switchgrass rhizosphere community habitats across a diverse set of soil and sampling environments. The methodology utilizes an outgroup of 28 non-switchgrass (other grasses and forbs) to identify a core switchgrass microbiome. Even across a diverse set of soils (five environments), and conservative statistical criteria (presence in more than 90% samples and FDR q-val <0.05% for Fisher's exact test) a core set of bacteria associated with switchgrass was observed. These included, among others, closely related taxa from Lysobacter spp., Mesorhizobium spp, and Chitinophagaceae. These bacteria have been shown to have functions related to the production of bacterial and fungal antibiotics and plant growth promotion. COREMIC can be used as a hypothesis generating or confirmatory tool that shows great potential for identifying taxa that may be irnportant to the functioning of a habitat (e.g. host plant). The case study, in conclusion, shows that COREMIC can identify key habitat-specific microbes across diverse samples, using currently available databases and a unique freely available software.
- High-performance biocomputing for simulating the spread of contagion over large contact networksBisset, Keith R.; Aji, Ashwin M.; Marathe, Madhav V.; Feng, Wu-chun (BMC, 2012-04-12)Background Many important biological problems can be modeled as contagion diffusion processes over interaction networks. This article shows how the EpiSimdemics interaction-based simulation system can be applied to the general contagion diffusion problem. Two specific problems, computational epidemiology and human immune system modeling, are given as examples. We then show how the graphics processing unit (GPU) within each compute node of a cluster can effectively be used to speed-up the execution of these types of problems. Results We show that a single GPU can accelerate the EpiSimdemics computation kernel by a factor of 6 and the entire application by a factor of 3.3, compared to the execution time on a single core. When 8 CPU cores and 2 GPU devices are utilized, the speed-up of the computational kernel increases to 9.5. When combined with effective techniques for inter-node communication, excellent scalability can be achieved without significant loss of accuracy in the results. Conclusions We show that interaction-based simulation systems can be used to model disparate and highly relevant problems in biology. We also show that offloading some of the work to GPUs in distributed interaction-based simulations can be an effective way to achieve increased intra-node efficiency.
- Identifying Transcriptional Regulatory Modules Among Different Chromatin States in Mouse Neural Stem CellsBanerjee, Sharmi; Zhu, Hongxiao; Tang, Man; Feng, Wu-chun; Wu, Xiaowei; Xie, Hehuang David (Frontiers, 2019-01-15)Gene expression regulation is a complex process involving the interplay between transcription factors and chromatin states. Significant progress has been made toward understanding the impact of chromatin states on gene expression. Nevertheless, the mechanism of transcription factors binding combinatorially in different chromatin states to enable selective regulation of gene expression remains an interesting research area. We introduce a nonparametric Bayesian clustering method for inhomogeneous Poisson processes to detect heterogeneous binding patterns of multiple proteins including transcription factors to form regulatory modules in different chromatin states. We applied this approach on ChIP-seq data for mouse neural stem cells containing 21 proteins and observed different groups or modules of proteins clustered within different chromatin states. These chromatin-state-specific regulatory modules were found to have significant influence on gene expression. We also observed different motif preferences for certain TFs between different chromatin states. Our results reveal a degree of interdependency between chromatin states and combinatorial binding of proteins in the complex transcriptional regulatory process. The software package is available on Github at - https://github.com/BSharmi/DPM-LGCP.
- Multi-dimensional characterization of electrostatic surface potential computation on graphics processors(2012-04-12)Background Calculating the electrostatic surface potential (ESP) of a biomolecule is critical towards understanding biomolecular function. Because of its quadratic computational complexity (as a function of the number of atoms in a molecule), there have been continual efforts to reduce its complexity either by improving the algorithm or the underlying hardware on which the calculations are performed. Results We present the combined effect of (i) a multi-scale approximation algorithm, known as hierarchical charge partitioning (HCP), when applied to the calculation of ESP and (ii) its mapping onto a graphics processing unit (GPU). To date, most molecular modeling algorithms perform an artificial partitioning of biomolecules into a grid/lattice on the GPU. In contrast, HCP takes advantage of the natural partitioning in biomolecules, which in turn, better facilitates its mapping onto the GPU. Specifically, we characterize the effect of known GPU optimization techniques like use of shared memory. In addition, we demonstrate how the cost of divergent branching on a GPU can be amortized across algorithms like HCP in order to deliver a massive performance boon. Conclusions We accelerated the calculation of ESP by 25-fold solely by parallelization on the GPU. Combining GPU and HCP, resulted in a speedup of at most 1,860-fold for our largest molecular structure. The baseline for these speedups is an implementation that has been hand-tuned SSE-optimized and parallelized across 16 cores on the CPU. The use of GPU does not deteriorate the accuracy of our results.
- Photonic Biosensor Assays to Detect and Distinguish Subspecies of Francisella tularensisCooper, Kristie L.; Bandara, Aloka B.; Wang, Yunmiao; Wang, Anbo; Inzana, Thomas J. (MDPI, 2011-03-07)The application of photonic biosensor assays to diagnose the category-A select agent Francisella tularensis was investigated. Both interferometric and long period fiber grating sensing structures were successfully demonstrated; both these sensors are capable of detecting the optical changes induced by either immunological binding or DNA hybridization. Detection was made possible by the attachment of DNA probes or immunoglobulins (IgG) directly to the fiber surface via layer-by-layer electrostatic self-assembly. An optical fiber biosensor was tested using a standard transmission mode long period fiber grating of length 15 mm and period 260 µm, and coated with the IgG fraction of antiserum to F. tularensis. The IgG was deposited onto the optical fiber surface in a nanostructured film, and the resulting refractive index change was measured using spectroscopic ellipsometry. The presence of F. tularensis was detected from the decrease of peak wavelength caused by binding of specific antigen. Detection and differentiation of F. tularensis subspecies tularensis (type A strain TI0902) and subspecies holarctica (type B strain LVS) was further accomplished using a single-mode multi-cavity fiber Fabry-Perot interferometric sensor. These sensors were prepared by depositing seven polymer bilayers onto the fiber tip followed by attaching one of two DNA probes: (a) a 101-bp probe from the yhhW gene unique to type-A strains, or (b) a 117-bp probe of the lpnA gene, common to both type-A and type-B strains. The yhhW probe was reactive with the type-A, but not the type-B strain. Probe lpnA was reactive with both type-A and type-B strains. Nanogram quantities of the target DNA could be detected, highlighting the sensitivity of this method for DNA detection without the use of PCR. The DNA probe reacted with 100% homologous target DNA, but did not react with sequences containing 2-bp mismatches, indicating the high specificity of the assay. These assays will fill an important void that exists for rapid, culture-free, and field-compatible diagnosis of F. tularensis.
- Retinal-input-induced epigenetic dynamics in the developing mouse dorsal lateral geniculate nucleusHe, Jianlin; Xu, Xiguang; Monavarfeshani, Aboozar; Banerjee, Sharmi; Fox, Michael A.; Xie, Hehuang David (2019-02-14)DNA methylation plays important roles in the regulation of nervous system development and in cellular responses to environmental stimuli such as light-derived signals. Despite great efforts in understanding the maturation and refinement of visual circuits, we lack a clear understanding of how changes in DNA methylation correlate with visual activity in the developing subcortical visual system, such as in the dorsal lateral geniculate nucleus (dLGN), the main retino-recipient region in the dorsal thalamus. Here, we explored epigenetic dynamics underlying dLGN development at ages before and after eye opening in wild-type mice and mutant mice in which retinal ganglion cells fail to form. We observed that development-related epigenetic changes tend to co-localize together on functional genomic regions critical for regulating gene expression, while retinal-input-induced epigenetic changes are enriched on repetitive elements. Enhancers identified in neurons are prone to methylation dynamics during development, and activity-induced enhancers are associated with retinal-input-induced epigenetic changes. Intriguingly, the binding motifs of activity-dependent transcription factors, including EGR1 and members of MEF2 family, are enriched in the genomic regions with epigenetic aberrations in dLGN tissues of mutant mice lacking retinal inputs. Overall, our study sheds new light on the epigenetic regulatory mechanisms underlying the role of retinal inputs on the development of mouse dLGN.
- Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young PersonsHixson, James E.; Jun, Goo; Shimmin, Lawrence C.; Wang, Yizhi; Yu, Guoqiang; Mao, Chunhong; Warren, Andrew S.; Howard, Timothy D.; Vander Heide, Richard S.; Van Eyk, Jennifer E.; Wang, Yue; Herrington, David M. (Springer Nature, 2017-06-22)We investigated the influence of genetic variants on atherosclerosis using whole exome sequencing in cases and controls from the autopsy study "Pathobiological Determinants of Atherosclerosis in Youth (PDAY)". We identified a PDAY case group with the highest total amounts of raised lesions (n = 359) for comparisons with a control group with no detectable raised lesions (n = 626). In addition to the standard exome capture, we included genome-wide proximal promoter regions that contain sequences that regulate gene expression. Our statistical analyses included single variant analysis for common variants (MAF > 0.01) and rare variant analysis for low frequency and rare variants (MAF < 0.05). In addition, we investigated known CAD genes previously identified by meta-analysis of GWAS studies. We did not identify individual common variants that reached exome-wide significance using single variant analysis. In analysis limited to 60 CAD genes, we detected strong associations with COL4A2/COL4A1 that also previously showed associations with myocardial infarction and arterial stiffness, as well as coronary artery calcification. Likewise, rare variant analysis did not identify genes that reached exomewide significance. Among the 60 CAD genes, the strongest association was with NBEAL1 that was also identified in gene-based analysis of whole exome sequencing for early onset myocardial infarction.