Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis

Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M.

doi:10.1186/1471-2105-10-200

Cited by 20 publications

(21 citation statements)

References 49 publications

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“…Pathway enrichment was conducted according to previously published methodologies (Simunovic, et al, 2009, Simunovic, et al, 2010, Yi, et al, 2009) using Biocarta, GOBP, GSEA, KEGG, and WIKI. Data mining was performed on published literature and using resources such as the MIRECORDS database (http://mirecords.umn.edu) (Xiao, et al, 2009), National Center for Adult Stem Cell Research - Parkinson’s Disease Review Database (https://ncascr.griffith.edu.au/pdreview/2009) and www.pdgene.org.…”

Section: Methodsmentioning

confidence: 99%

miR-126 contributes to Parkinson's disease by dysregulating the insulin-like growth factor/phosphoinositide 3-kinase signaling

Kim

Lee

McKenna

et al. 2014

Neurobiology of Aging

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126

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Dopamine (DA) neurons in sporadic Parkinson disease (PD) display dysregulated gene expression networks and signaling pathways that are implicated in PD pathogenesis. Micro (mi)RNAs are regulators of gene expression, which could be involved in neurodegenerative diseases. We determined the miRNA profiles in laser microdissected DA neurons from postmortem sporadic PD patients’ brains and age-matched controls. DA neurons had a distinctive miRNA signature and a set of miRNAs was dysregulated in PD. Bioinformatics analysis provided evidence for correlations of miRNAs with signaling pathways relevant to PD, including an association of miR-126 with insulin/IGF-1/PI3K signaling. In DA neuronal cell systems, enhanced expression of miR-126 impaired IGF-1 signaling and increased vulnerability to the neurotoxin 6-OHDA by downregulating factors in IGF-1/PI3K signaling, including its targets p85β, IRS-1, and SPRED1. Blocking of miR-126 function increased IGF-1 trophism and neuroprotection to 6-OHDA. Our data imply that elevated levels of miR-126 may play a functional role in DA neurons and in PD pathogenesis by downregulating IGF-1/PI3K/AKT signaling and that its inhibition could be a mechanism of neuroprotection.

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Section: Methodsmentioning

confidence: 99%

miR-126 contributes to Parkinson's disease by dysregulating the insulin-like growth factor/phosphoinositide 3-kinase signaling

Kim

Lee

McKenna

et al. 2014

Neurobiology of Aging

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126

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“…The gene lists for each sample were entered into our pattern extraction pipeline analysis (PPEP) [101], as implemented in the WPS package [102], to obtain the ListHit of genes (number of genes from each list that are annotated to each pathway) for each of the BioCarta pathways. For each tumor type, each pathway was ranked on the basis of how frequently it was “hit” by individual patient samples and the ranking scores were obtained as the percentages of patient samples that had at least one hit in the corresponding pathway, using customized R scripts.…”

Section: Methodsmentioning

confidence: 99%

Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited Disease

Bacolla

Temiz

et al. 2013

PLoS Genet

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Single base substitutions constitute the most frequent type of human gene mutation and are a leading cause of cancer and inherited disease. These alterations occur non-randomly in DNA, being strongly influenced by the local nucleotide sequence context. However, the molecular mechanisms underlying such sequence context-dependent mutagenesis are not fully understood. Using bioinformatics, computational and molecular modeling analyses, we have determined the frequencies of mutation at G•C bp in the context of all 64 5′-NGNN-3′ motifs that contain the mutation at the second position. Twenty-four datasets were employed, comprising >530,000 somatic single base substitutions from 21 cancer genomes, >77,000 germline single-base substitutions causing or associated with human inherited disease and 16.7 million benign germline single-nucleotide variants. In several cancer types, the number of mutated motifs correlated both with the free energies of base stacking and the energies required for abstracting an electron from the target guanines (ionization potentials). Similar correlations were also evident for the pathological missense and nonsense germline mutations, but only when the target guanines were located on the non-transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly affected positions in which a purine was located on the non-transcribed DNA strand. Novel candidate driver mutations and tissue-specific mutational patterns were also identified in the cancer datasets. We conclude that electron transfer reactions within the DNA molecule contribute to sequence context-dependent mutagenesis, involving both somatic driver and passenger mutations in cancer, as well as germline alterations causing or associated with inherited disease.

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“…To predict the complement of transcription factors involved in Pi response, we identified the transcription factor binding elements that are enriched in the promoters of Pi responsive genes. The Pathway Pattern Extraction Pipeline (PPEP) method (Yi et al, 2009) provided by the in‐house tool WholePathwayScope (Yi et al, 2006) was used to define and compare the enrichment of transcription factor binding elements within the promoters of Pi‐responsive genes across the time course of experiments. Northern blotting suggested the “early” genes (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…enrichment in the user's gene lists. We then used the newly developed PPEP method (Yi et al, 2009) in WPS to perform pathway‐level comparative analysis on the differential gene lists derived for each of the time points across the 72 h time course (Fig. S1A).…”

Section: Methodsmentioning

confidence: 99%

“…MATCH program was used to search for transcription binding sites within positions −1500 and +200 of transcription initiation sites of all annotated genes in the mouse genome. Based on these predicted target genes of transcription factors, comparative analysis of the enrichment levels of transcription factor target genes within the differentiated lists obtained from the time‐course experiments were performed using PPEP method (Yi et al, 2009). …”

Section: Methodsmentioning

confidence: 99%

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Is it the end of the line for the EMT?

Kisseleva

Brenner

2011

Hepatology

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E pithelial-to-mesenchymal transition (EMT) is an important biological concept that describes the reversible transition of differentiated epithelial cells into mesenchymal cells with increased motility and changes in gene expression. Three types of EMT have been proposed: Type 1 EMT describes the invasion of transition cells into the mesenchyme during development. Type 2 EMT describes the transition into mesenchymal cells, potentially including myofibroblasts during wound healing and repair. Type 3 EMT describes invasion of cancer cells, including those migrating into the circulation to generate distant metastases. 1Fibrosis studies conducted in different organs including the liver have demonstrated that myofibroblasts are the primary source of extracellular matrix.2 Myofibroblasts are immunophenotypically characterized by a stellate shape, expression of abundant pericellular matrix, and fibrotic genes (a-smooth muscle actin [a-SMA], nonmuscle myosin, fibronectin, vimentin).3 Ultrastructurally, myofibroblasts are defined by prominent rough endoplasmic reticulum, a Golgi apparatus producing collagen, peripheral myofilaments, fibronexus (no lamina), and gap junctions.3 Myofibroblasts are implicated in wound healing and fibroproliferative disorders. [4][5][6] In response to fibrogenic stimuli, such as transforming growth factor b1 (TGF-b1), myofibroblasts express a-SMA, secrete extracellular matrix (fibronectin, collagen type I and III), obtain high contractility, and change phenotype (production of the stress fibers). 7But where do these myofibroblasts come from? Hepatic stellate cells (HSCs) are considered to be a major source of fibrogenic myofibroblasts in the injured liver. Hepatic myofibroblasts may also originate from portal fibroblasts, 2 bone marrow-derived mesenchymal cells, and fibrocytes, 9,10 and by the transition of epithelial cells 11 and endothelial cells 12 to mesenchymal cells. What is the evidence for type 2 EMT being the etiology of the myofibroblasts in liver fibrosis? First, multiple studies in the kidney and in the lung were interpreted as showing EMT during fibrosis in those organs, and this concept was extrapolated to liver fibrosis (discussed in Zeisberg and Duffield 13 ). Second, primary cell culture studies have clearly demonstrated that cholangiocytes and hepatocytes undergo a change in the phenotype and gene expression toward a mesenchymal cell, especially after incubation with TGF-beta, which is the cytokine most closely associated with EMT.14 Third, immunohistochemical studies both in experimental and clinical liver fibrosis have reported the coexpression of mesenchymal markers (fibroblastspecific protein 1 [FSP1], a-SMA, vimentin, desmin) with the original epithelial markers (cytokeratin-19 for cholangiocytes and albumin for hepatocytes).15 These types of studies have been recently questioned, because the allegedly EMT-specific marker FSP1 (also called S100A4) has now been shown to be expressed by nonfibroblast cells in the liver, including by a subset of monocytes.16 Fourth, at lea...

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Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis

Cited by 20 publications

References 49 publications

miR-126 contributes to Parkinson's disease by dysregulating the insulin-like growth factor/phosphoinositide 3-kinase signaling

miR-126 contributes to Parkinson's disease by dysregulating the insulin-like growth factor/phosphoinositide 3-kinase signaling

Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited Disease

Is it the end of the line for the EMT?

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