Dact gene expression profiles suggest a role for this gene family in integrating Wnt and TGF-β signaling pathways during chicken limb development

AbstractFor breast cancer, clinically important subtypes are well characterised at the molecular level in terms of gene expression profiles. In addition, signaling pathways in breast cancer have been extensively studied as therapeutic targets due to their roles in tumor growth and metastasis. However, it is challenging to put signaling pathways and gene expression profiles together to characterise biological mechanisms of breast cancer subtypes since many signaling events result from post-translational modifications, rather than gene expression differences.We present a logic-based approach to explain the differences in gene expression profiles among breast cancer subtypes using Pathway Logic and transcriptional network information. Pathway Logic is a rewriting-logic-based formal system for modeling biological pathways including post-translational modifications. Proposed method demonstrated its utility by constructing subtype-specific path from key receptors (TNFR, TGFBR1 and EGFR) to key transcription factor (TF) regulators (RELA, ATF2, SMAD3 and ELK1) and identifying potential pathway crosstalk via TFs in basal-specific paths, which could provide a novel insight on aggressive breast cancer subtypes.AvailabilityAnalysis result is available at http://epigenomics.snu.ac.kr/PL/

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Transcription Profiles Associated with Inducible Adhesion in Candida parapsilosis

mSphere ◽

10.1128/msphere.01071-20 ◽

2021 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Joseph M. Bliss ◽

George A. Tollefson ◽

Abigail Cuevas ◽

Sarah J. Longley ◽

Matthew N. Neale ◽

...

Keyword(s):

Gene Expression ◽

Gene Family ◽

Candida Parapsilosis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Enrichment Analysis ◽

Gene Families ◽

Mammalian Host ◽

Emerging Infections ◽

Content Type

ABSTRACT Candida parapsilosis has emerged as a frequent cause of invasive candidiasis with increasing evidence of unique biological features relative to C. albicans. As it adapts to conditions within a mammalian host, rapid changes in gene expression are necessary to facilitate colonization and persistence in this environment. Adhesion of the organism to biological surfaces is a key first step in this process and is the focus of this study. Building on previous observations showing the importance of a member of the ALS gene family in C. parapsilosis adhesion, three clinical isolates were cultured under two conditions that mimic the mammalian host and promote adhesion, incubation at 37°C in tissue culture medium 199 or in human plasma. Transcriptional profiles using RNA-seq were obtained in these adhesion-inducing conditions and compared to profiles following growth in yeast media that suppress adhesion to identify gene expression profiles associated with adhesion. Overall gene expression profiles among the three strains were similar in both adhesion-inducing conditions and distinct from adhesion-suppressing conditions. Pairwise analysis among the three growth conditions identified 133 genes that were differentially expressed at a cutoff of ±4-fold, with the most upregulated genes significantly enriched in iron acquisition and transmembrane transport, while the most downregulated genes were enriched in oxidation-reduction processes. Gene family enrichment analysis identified gene families with diverse functions that may have an important role in this important step for colonization and disease. IMPORTANCE Invasive Candida infections are frequent complications of the immunocompromised and are associated with substantive morbidity and mortality. Although C. albicans is the best-studied species, emerging infections by non-albicans Candida species have led to increased efforts to understand aspects of their pathogenesis that are unique from C. albicans. C. parapsilosis is a frequent cause of invasive infections, particularly among premature infants. Recent efforts have identified important virulence mechanisms that have features distinct from C. albicans. C. parapsilosis can exist outside a host environment and therefore requires rapid modifications when it encounters a mammalian host to prevent its clearance. An important first step in the process is adhesion to host surfaces. This work takes a global, nonbiased approach to investigate broad changes in gene expression that accompany efficient adhesion. As such, biological pathways and individual protein targets are identified that may be amenable to manipulation to reduce colonization and disease from this organism.

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Identification of distinctive patterns in cell signaling pathways in glioblastoma multiforme subtypes using gene expression TCGA data sets.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23162 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23162-e23162

Author(s):

Konstantin Volyanskyy ◽

Minghao Zhong ◽

Payal Keswarpu ◽

John T Fallon ◽

Michael Paul Fanucchi ◽

...

Keyword(s):

Gene Expression ◽

Cell Signaling ◽

Signaling Pathways ◽

Normal Tissue ◽

Gene Selection ◽

Molecular Subtype ◽

Expression Profiles ◽

Gene Expression Profiles ◽

The Cancer Genome Atlas ◽

Cell Signaling Pathways

e23162 Background: Cancer is characterized by a variety of heterogeneous genomic and transcriptomic patterns involving highly complex signaling biological pathways. The problem of identification of the factors driving tumor progression becomes even more challenging due to intricate interaction mechanisms between these pathways. Using novel approaches in machine learning, we demonstrate the ability to quantitatively describe characteristic signaling patterns in cancer based on transcriptomic data Methods: We used RNASeq data from 20531 genes in 174 samples of GBM from The Cancer Genome Atlas including 5 major histological subtypes – Classical, G-CIMP, Mesenchymal, Neural, and Proneural, anddeveloped predictive computational framework for molecular subtype differentiation from normal tissue relying on variance based gene selection and random forest algorithm. Results: We obtained a few key findings – (1) genes from cell signaling pathways alone differentiate each subtype from normal tissue with 100% accuracy; (2) predictive genes are specific to each subtype; (3) inferred pathway interactions are also specific to each subtype; (4) typically most of the predictive genes involved in signaling are down-regulated in tumor compared to normal tissue (MAPT, PRKCG, PDE2A, RYR2, ATP1B1, GRN1, GNAO1), however, in each subtype we observed a smaller subset of predictive genes which are highly up-regulated in tumor (ID3, FN1, JAG1, F2R, COL4A1, EDAR, CDK2, CDK4, MFNG, BIRC5, CCNB2). We detected and quantitatively evaluated characteristic signaling pathway involvement across the GBM subtypes for MAPK, RAP1, RAS, Notch, PI3K-Akt, mTOR, FoxO, Jak-STAT, Wnt, cAMP, and Calcium Signaling, providing a unique approximation for each subtype signaling profile. Conclusions: In this study, we identified gene expression profiles and associated signaling pathways for distinguishing GBM Multiforme subtypes from normal tissue. We observed and described a dense complex picture of interacting signaling pathways. The detected interactions may provide clinical insights and could be used to identify potential therapeutic targets, however, more research is needed to confirm this.

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Comparison of the Gene Expression Profiles of Human Fetal Cortical Astrocytes with Pluripotent Stem Cell Derived Neural Stem Cells Identifies Human Astrocyte Markers and Signaling Pathways and Transcription Factors Active in Human Astrocytes

PLoS ONE ◽

10.1371/journal.pone.0096139 ◽

2014 ◽

Vol 9 (5) ◽

pp. e96139 ◽

Cited By ~ 22

Author(s):

Nasir Malik ◽

Xiantao Wang ◽

Sonia Shah ◽

Anastasia G. Efthymiou ◽

Bin Yan ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Stem Cell ◽

Transcription Factors ◽

Neural Stem Cells ◽

Signaling Pathways ◽

Pluripotent Stem Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Human Astrocytes

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Integrative analysis of gene expression profiles reveals specific signaling pathways associated with pancreatic duct adenocarcinoma

Cancer Communications ◽

10.1186/s40880-018-0289-9 ◽

2018 ◽

Vol 38 (1) ◽

pp. 13 ◽

Cited By ~ 4

Author(s):

Jun Li ◽

Wenle Tan ◽

Linna Peng ◽

Jialiang Zhang ◽

Xudong Huang ◽

...

Keyword(s):

Gene Expression ◽

Pancreatic Duct ◽

Signaling Pathways ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Integrative Analysis ◽

Pancreatic Duct Adenocarcinoma

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Gene Expression Profiles for Prognosis in MGUS, Coupled with Signatures of Oncogenic Pathway Deregulation Provide a Novel Approach for Selection of Molecular Targets in Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.655.655 ◽

2007 ◽

Vol 110 (11) ◽

pp. 655-655

Author(s):

Ariel Anguiano ◽

Chaitanya Acharya ◽

Kelly Salter ◽

Daniel McCluskey ◽

Christina Gasperetto ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Signaling Pathways ◽

Chromosomal Instability ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Oncogenic Pathways ◽

Novel Approach ◽

Pathway Activation ◽

Plasma Cell Dyscrasias

Abstract Gene expression profiles that reflect unique aspects of biologic phenotypes and characterize the heterogeneity of monoclonal gammopathies may facilitate the development of a ‘signature’ that predicts the evolution of MGUS to multiple myeloma (MM). Furthermore, while most patients with MM are initially sensitive to therapy, resistance invariably develops. Thus, a need exits for novel therapeutic strategies targeting resistance-associated deregulated molecular pathways. Using previously-described methodologies that employ DNA microarray data in a cohort of 877 annotated samples from patients with plasma cell dyscrasias (MGUS, untreated MM and refractory MM), a complex multi-gene expression profile (‘metagene’) of 120 genes was identified that predicts risk of progression, from MGUS to MM. This analysis used an initial ‘test’ cohort of patients with MGUS that represented patients followed for a median of 36.4 months. At follow up, 11% of these patients were identified as having disease progression. Leave-one-out cross validation analysis within the test cohort revealed 95% accuracy. The ‘metagene model’ was also evaluated in a large independent validation cohort. Overexpressed genes in the predictive model represented those involved in the proteasome, RAS, and MAP-kinase pathways. In addition, we used gene expression signatures that reflect the deregulation of major oncogenic signaling pathways (Ras, PI3kinase, Akt, Src, ß-catenin, E2F, and Myc) and pathways representative of the tumor microenvironment (Hypoxia, Angiogenesis, Chromosomal Instability, and TNF-alpha) to identify patterns of pathway activation unique to individual patients with plasma cell dyscrasias. This analysis revealed that patterns of pathway activation clearly defined the stages of myeloma progression. As an example, Myc deregulation was unique to refractory MM (p < 0.001) as compared to Ras and PI3K activation in MGUS patients (p < 0.01). Also, unique to refractory MM, a majority of the tumors (> 96%) had deregulation of multiple signaling pathways, suggesting a complex oncogenic process. In particular, these samples demonstrated deregulation in Ras (78%), Myc (70%), Src (63%), E2F (52%) and ß-catenin (52%) pathways. In contrast, normal plasma cells showed none to minimal deregulation of the oncogenic pathways. As a proof of concept, we then used cell proliferation assays to show that the predicted deregulation of Ras, Src and PI3 kinase pathways was directly proportional (p < 0.01, log rank test) to the sensitivity of cell lines (n = 17) to agents (FTS, SU6656, and LY4002 respectively) that specifically target these pathways. This suggests that in addition to identifying a high-risk cohort of patients with MGUS, such a strategy provides a novel approach to targeted therapeutics in refractory MM - by guiding the appropriate use of pathway specific inhibitors. Finally, results of Kaplan Meier analyses using gene expression-based classifiers and risk stratification models as well as further in vitro data involving manipulation of other oncogenic pathways and signatures relevant to myeloma (e.g. hypoxia, chromosomal instability and angiogenesis) will be also be presented.

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The SAL-PAP Chloroplast Retrograde Pathway Contributes to Plant Immunity by Regulating Glucosinolate Pathway and Phytohormone Signaling

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-03-17-0055-r ◽

2017 ◽

Vol 30 (10) ◽

pp. 829-841 ◽

Cited By ~ 20

Author(s):

Yasuhiro Ishiga ◽

Mutsumi Watanabe ◽

Takako Ishiga ◽

Takayuki Tohge ◽

Takakazu Matsuura ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Pseudomonas Syringae ◽

Expression Profiles ◽

Plant Immunity ◽

Gene Expression Profiles ◽

Nuclear Gene ◽

Retrograde Signaling ◽

Necrotrophic Pathogen ◽

Nuclear Gene Expression

Chloroplasts have a crucial role in plant immunity against pathogens. Increasing evidence suggests that phytopathogens target chloroplast homeostasis as a pathogenicity mechanism. In order to regulate the performance of chloroplasts under stress conditions, chloroplasts produce retrograde signals to alter nuclear gene expression. Many signals for the chloroplast retrograde pathway have been identified, including chlorophyll intermediates, reactive oxygen species, and metabolic retrograde signals. Although there is a reasonably good understanding of chloroplast retrograde signaling in plant immunity, some signals are not well-understood. In order to understand the role of chloroplast retrograde signaling in plant immunity, we investigated Arabidopsis chloroplast retrograde signaling mutants in response to pathogen inoculation. sal1 mutants (fry1-2 and alx8) responsible for the SAL1-PAP retrograde signaling pathway showed enhanced disease symptoms not only to the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000 but, also, to the necrotrophic pathogen Pectobacterium carotovorum subsp. carotovorum EC1. Glucosinolate profiles demonstrated the reduced accumulation of aliphatic glucosinolates in the fry1-2 and alx8 mutants compared with the wild-type Col-0 in response to DC3000 infection. In addition, quantification of multiple phytohormones and analyses of their gene expression profiles revealed that both the salicylic acid (SA)- and jasmonic acid (JA)-mediated signaling pathways were down-regulated in the fry1-2 and alx8 mutants. These results suggest that the SAL1-PAP chloroplast retrograde pathway is involved in plant immunity by regulating the SA- and JA-mediated signaling pathways.

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Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways

Blood ◽

10.1182/blood-2014-07-591461 ◽

2015 ◽

Vol 125 (1) ◽

pp. 133-139 ◽

Cited By ~ 48

Author(s):

Stefan Gröschel ◽

Mathijs A. Sanders ◽

Remco Hoogenboezem ◽

Annelieke Zeilemaker ◽

Marije Havermans ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Signaling Pathways ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Entity ◽

Rtk Signaling ◽

Mutational Spectrum ◽

Epigenetic Modifier ◽

Key Points

Key Points inv(3)/t(3;3) disease exhibits high rates of activated RAS/RTK signaling, epigenetic modifier, splice, and transcription factor mutations. AML and MDS with inv(3)/t(3;3) display similar mutational and gene expression profiles and should be considered a single molecular entity.

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