michael welge - Academia.edu (original) (raw)

Papers by michael welge

Genome Research, Apr 2, 2009

The persistence of large blocks of homologous synteny and a high frequency of breakpoint reuse ar... more The persistence of large blocks of homologous synteny and a high frequency of breakpoint reuse are distinctive features of mammalian chromosomes that are not well understood in evolutionary terms. To gain a better understanding of the evolutionary forces that affect genome architecture, synteny relationships among 10 amniotes (human, chimp, macaque, rat, mouse, pig, cattle, dog, opossum, and chicken) were compared at <1 human-Mbp resolution. Homologous synteny blocks (HSBs; N = 2233) and chromosome evolutionary breakpoint regions (EBRs; N = 1064) were identified from pairwise comparisons of all genomes. Analysis of the size distribution of HSBs shared in all 10 species' chromosomes (msHSBs) identified three (>20 Mbp) that are larger than expected by chance. Gene network analysis of msHSBs >3 human-Mbp and EBRs <1 Mbp demonstrated that msHSBs are significantly enriched for genes involved in development of the central nervous and other organ systems, whereas EBRs are enriched for genes associated with adaptive functions. In addition, we found EBRs are significantly enriched for structural variations (segmental duplications, copy number variants, and indels), retrotransposed and zinc finger genes, and single nucleotide polymorphisms. These results demonstrate that chromosome breakage in evolution is nonrandom and that HSBs and EBRs are evolving in distinctly different ways. We suggest that natural selection acts on the genome to maintain combinations of genes and their regulatory elements that are essential to fundamental processes of amniote development and biological organization. Furthermore, EBRs may be used extensively to generate new genetic variation and novel combinations of genes and regulatory elements that contribute to adaptive phenotypes.

We present an application of genetic algorithmbased design to configuration of high-level optimiz... more We present an application of genetic algorithmbased design to configuration of high-level optimization systems, or wrappers, for relevance determination and constructive induction. Our system combines genetic wrappers with elicited knowledge on attribute relevance and synthesis. We discuss decision support issues in a largescale commercial data mining project (cost prediction for multiple automobile insurance markets), and report experiments using D2K, a Java-based visual programming system for data mining and information visualization, and several commercial and research tools. Our GA system, Jenesis [HWRC00], is deployed on several network-of-workstation systems (Beowulf clusters). It achieves a linear speedup, due to a high degree of task parallelism, and improved test set accuracy, compared to decision tree learning with only constructive induction and state-space search-based wrappers [KJ97].

Page 1. Self-organizing Systems for Knowledge Discovery in Large Databases William H. Hsu, Lorett... more Page 1. Self-organizing Systems for Knowledge Discovery in Large Databases William H. Hsu, Loretta S. Auvil, William M. Pottenger, David Tcheng, and Michael Welge .f bhsu I lauvil I bib I dtchene I welee Mii2ncsa.uiuc.edu ...

Genes, Feb 4, 2020

The hippocampus is involved in learning and memory and undergoes significant growth and maturatio... more The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental timeframe can have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation and gene transcription from two independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and porcine reproductive and respiratory syndrome virus (PRRSv) infection) using porcine biomedical models. In total, 420 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, including genes involved in neurodevelopment and function. Gene ontology (GO) terms enriched for DEGs were associated with immune responses, angiogenesis, and cellular development. In addition, 116 differentially methylated regions (DMRs) were identified, which overlapped 125 genes. While no GO terms were enriched for genes overlapping DMRs, many of these genes are known to be involved in neurodevelopment and function, angiogenesis, and immunity. The observed altered methylation and expression of genes involved in neurological function suggest reduced cognition in response to early life environmental insults is due to altered cholinergic signaling and calcium regulation. Finally, two DMRs overlapped with two DEGs, VWF and LRRC32, which are associated with blood brain barrier permeability and regulatory T-cell activation, respectively. These results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally-induced reductions in cognitive development across independent studies.

AGU Fall Meeting Abstracts, Dec 1, 2004

NCSA's goal is to create a balanced system that fully supports high-end computing as well as... more NCSA's goal is to create a balanced system that fully supports high-end computing as well as: 1) high-end data management and analysis; 2) visualization of massive, highly complex data collections; 3) large databases; 4) geographically distributed Grid computing; and 5) collaboratories, all based on a secure computational environment and driven with workflow-based services. To this end NCSA has defined a new technology path that includes the integration and provision of cyberservices in support of data analysis, mining, and visualization. NCSA has begun to develop and apply a data mining system-NCSA Data-to-Knowledge (D2K)-in conjunction with both the application and research communities. NCSA D2K will enable the formation of model-based application workflows and visual programming interfaces for rapid data analysis. The Java-based D2K framework, which integrates analytical data mining methods with data management, data transformation, and information visualization tools, will be configurable from the cyberservices (web and grid services, tools, ..) viewpoint to solve a wide range of important data mining problems. This effort will use modules, such as a new classification methods for the detection of high-risk geoscience events, and existing D2K data management, machine learning, and information visualization modules. A D2K cyberservices interface will be developed to seamlessly connect client applications with remote back-end D2K servers, providing computational resources for data mining and integration with local or remote data stores. This work is being coordinated with SDSC's data and services efforts. The new NCSA Visualization embedded workflow environment (NVIEW) will be integrated with D2K functionality to tightly couple informatics and scientific visualization with the data analysis and management services. Visualization services will access and filter disparate data sources, simplifying tasks such as fusing related data from distinct sources into a coherent visual representation. This approach enables collaboration among geographically dispersed researchers via portals and front-end clients, and the coupling with data management services enables recording associations among datasets and building annotation systems into visualization tools and portals, giving scientists a persistent, shareable, virtual lab notebook. To facilitate provision of these cyberservices to the national community, NCSA will be providing a computational environment for large-scale data assimilation, analysis, mining, and visualization. This will be initially implemented on the new 512 processor shared memory SGI's recently purchased by NCSA. In addition to standard batch capabilities, NCSA will provide on-demand capabilities for those projects requiring rapid response (e.g., development of severe weather, earthquake events) for decision makers. It will also be used for non-sequential interactive analysis of data sets where it is important have access to large data volumes over space and time.

Springer eBooks, 1989

The response of a complex system is usually very complicated if it is perturbed by a sinusiodal d... more The response of a complex system is usually very complicated if it is perturbed by a sinusiodal driving force. We show, however, that for every complex system there is a special aperiodic driving force which produces a simple response. This special driving force is related to a certain nonlinear differential equation. We propose to use the parameters of this differential equation to describe the complexity of the system.

This paper builds introduces visual-analytic techniques to aggregate, summarize, and visualize th... more This paper builds introduces visual-analytic techniques to aggregate, summarize, and visualize the information generated during interactive evolutionary processes. Special visualizations of the user-provided partial ordering of solutions, the synthetic fitness surrogates induced, and the model of user preferences were prepared. The proposed visualanalytic techniques point out potential pitfalls, strengths, and possible improvements in a non-trivial case study where the hierarchical tournament selection scheme of an active interactive genetic algorithm is replaced by an incremental selection scheme. Visual analytics provided an intuitive reasoning environment that unveiled important properties that greatly affect the performance of active interactive genetic algorithms that could not have been easily reveled otherwise.

Data-intensive flow computing allows efficient processing of large volumes of data otherwise unap... more Data-intensive flow computing allows efficient processing of large volumes of data otherwise unapproachable. This paper introduces a new semantic-driven data-intensive flow infrastructure which: (1) provides a robust and transparent scalable solution from a laptop to large-scale clusters,(2) creates an unified solution for batch and interactive tasks in high-performance computing environments, and (3) encourages reusing and sharing components. Banking on virtualization and cloud computing techniques the Meandre infrastructure is able to create and dispose Meandre clusters on demand, being transparent to the final user. This paper also presents a prototype of such clustered infrastructure and some results obtained using it.

... 62 (1989) (c) 1989 Birkhäuser Verlag, Basel ADAPTIVE CONTROL OF CHAOTIC SYSTEMS A. Hübler Ins... more ... 62 (1989) (c) 1989 Birkhäuser Verlag, Basel ADAPTIVE CONTROL OF CHAOTIC SYSTEMS A. Hübler Institut für Theoretische Physik und Synergetik, Universität ...

Scientific Reports, 2018

In this study, sequencing of the 16S rRNA gene targeting the V4-V6 regions was conducted to asses... more In this study, sequencing of the 16S rRNA gene targeting the V4-V6 regions was conducted to assess the cecal microbial alterations in response to dietary supplementation with a yeast derived mannan rich fraction (MRF) in standard commercial broiler production settings across four separate broiler trials. The resulting data was analysed to identify consistent changes in the bacterial community structure of the broiler cecum in response to MRF supplementation. Subsequently, the datasets from each individual trial were pooled and analysed for differences between control and MRF supplemented diets at day 35 posthatch. The results from this analysis showed that Phylum Firmicutes was decreased and Phylum Bacteroidetes was increased across all four trials at day 35 posthatch when compared to the control. An extension of the random forest bioinformatics approach to discover a highly relevant set of microbial operational taxonomic units (OTUs) which are indicative of MRF supplementation in t...

ABSTRACTGut microbiome-host interactions play a crucial role in health and disease. Altered gut m... more ABSTRACTGut microbiome-host interactions play a crucial role in health and disease. Altered gut microbiome composition has been observed in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), a disorder characterized by pelvic pain, voiding dysfunction, and often co-morbid with anxiety/depression. We recently showed that mice deficient for acyloxyacyl hydrolase (AOAH) mimic pelvic pain symptoms and comorbidities of IC/BPS and also exhibit gut dysbiosis. In addition, we previously identified that the conditional knockout (cKO) of two transcriptional regulators of the gene encoding corticotropin-releasing factor, Crf, that are downstream of AOAH, aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor-γ (PPARγ), alleviate anxiety/depressive and voiding phenotypes of AOAH-deficient mice. Here, we examined the effects of AhR and PPARγ in CRF-expressing cells on the dysbiosis of AOAH-deficiency. AOAH-deficient mice with cKO of PPARγ and AhR/PPARγ ex...

Circulation, 2015

Introduction: Myxomatous mitral valve disease (MMVD) is a degenerative condition characterized by... more Introduction: Myxomatous mitral valve disease (MMVD) is a degenerative condition characterized by tissue fibrosis and matrix remodeling which ultimately progresses to leaflet prolapse. While recent work has shown that transforming growth factor beta (TGF-β) signaling contributes to the pathogenesis of MMVD, upstream regulators of this and other pathways remain poorly understood. Hypothesis: We sought to use high-throughput RNA sequencing coupled with microRNA (miRNA) sequencing to identify novel molecular targets as well as upstream regulators contributing to MMVD. Methods: We conducted mRNA and miRNA sequencing on normal (n = 10) and myxomatous human mitral valve samples (n = 10). Differential expression was identified using linear modeling and parallel random forest analyses. Canonical pathways were identified by Ingenuity Pathway Analyses (IPA). Predicted miRNA targets were identified using TargetScanHuman 6.2. Results: We found 2784 mRNAs that were differentially expressed betwe...

Supplementary data and figures for Rahman-Enyart et al., 2021. These files include 16S and metabo... more Supplementary data and figures for Rahman-Enyart et al., 2021. These files include 16S and metabolomics data comparing wild-type and AOAH-deficient mice ceca.

The FASEB Journal, 2016

BackgroundA growing body of literature supports the ability of specific foods and nutrients to im... more BackgroundA growing body of literature supports the ability of specific foods and nutrients to impact the gastrointestinal microbiome. However, there is a dearth of knowledge on the interplay of di...

Scientific Reports, 2020

Screening agrochemicals and pharmaceuticals for potential liver toxicity is required for regulato... more Screening agrochemicals and pharmaceuticals for potential liver toxicity is required for regulatory approval and is an expensive and time-consuming process. The identification and utilization of early exposure gene signatures and robust predictive models in regulatory toxicity testing has the potential to reduce time and costs substantially. In this study, comparative supervised machine learning approaches were applied to the rat liver TG-GATEs dataset to develop feature selection and predictive testing. We identified ten gene biomarkers using three different feature selection methods that predicted liver necrosis with high specificity and selectivity in an independent validation dataset from the Microarray Quality Control (MAQC)-II study. Nine of the ten genes that were selected with the supervised methods are involved in metabolism and detoxification (Car3, Crat, Cyp39a1, Dcd, Lbp, Scly, Slc23a1, and Tkfc) and transcriptional regulation (Ablim3). Several of these genes are also im...

Urologic chronic pelvic pain syndrome patients include men chronic prostatitis/chronic pelvic pai... more Urologic chronic pelvic pain syndrome patients include men chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and patients, mainly women, with interstitial cystitis/bladder pain syndrome (IC/BPS or IC). CP/CPPS is marked by severe chronic pelvic pain of unknown etiology that is differentially associated with prostatic inflammation. Microbes are known to modulate sensory responses, and microbiota are increasingly understood to drive normal biological processes and pathogenesis, including inflammation. Recent studies have linked fecal dysbiosis with chronic pelvic pain in IC/BPS, suggesting a role for microbiota in modulating UCPPS pain. Similarly, dysbiosis has been reported in CP/CPPS patients, but the relationship between with the dysbiosis of IC/BPS patients is unclear. Here, we characterized the fecal microbiota of men with CP/CPPS and women and men with IC/BPS. Similar to recent reports, we identified fecal dysbiosis in men with CP/CPPS relative to healthy controls among...

Lecture Notes in Computer Science, 2011

The volumes and velocity of data are growing at unprecedented rates, often physically distributed... more The volumes and velocity of data are growing at unprecedented rates, often physically distributed, have access constraints, and requirements to leverage the diverse computational fabrics like clouds and grids. The Meandre data-intensive component-based application infrastructure can leverage diversity and enables extremely scalable server clusters and applications to address these challenges. Data-intensive flows can: be web-services and/or computational tasks; co-locate processing with data; orchestrate cloud computing resources; and leverage grid resources with distributed execution. Meandre from a laptop to a cloud, grid, or server as analytical computational tasks and/or web-services in data-intensive flows made up of components that provide deployment and execution strategies for extreme scalability.

2008 IEEE Fourth International Conference on eScience, 2008