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An Integrative Approach for Mapping Differentially Expressed Genes and Network Components Using Novel Parameters to Elucidate Key Regulatory Genes in Colorectal Cancer.

ABSTRACT: For examining the intricate biological processes concerned with colorectal cancer (CRC), a systems biology approach integrating several biological components and other influencing factors is essential to understand. We performed a comprehensive system level analysis for CRC which assisted in unravelling crucial network components and many regulatory elements through a coordinated view. Using this integrative approach, the perceptive of complexity hidden in a biological phenomenon is extensively simplified. The microarray analyses facilitated differential expression of 631 significant genes employed in the progression of disease and supplied interesting associated up and down regulated genes like jun, fos and mapk1. The transcriptional regulation of these genes was deliberated widely by examining transcription factors such as hnf4, nr2f1, znf219 and dr1 which directly influence the expression. Further, interactions of these genes/proteins were evaluated and crucial network motifs were detected to associate with the pathophysiology of CRC. The available standard statistical parameters such as z-score, p-value and significance profile were explored for the identification of key signatures from CRC pathway whereas a few novel parameters representing over-represented structures were also designed in the study. The applied approach revealed 5 key genes i.e. kras, araf, pik3r5, ralgds and akt3 via our novel designed parameters illustrating high statistical significance. These novel parameters can assist in scrutinizing candidate markers for diseases having known biological pathways. Further, investigating and targeting these proposed genes for experimental validations, instead being spellbound by the complicated pathway will certainly endow valuable insight in a well-timed systematic understanding of CRC.

SUBMITTER: Sehgal M

PROVIDER: S-EPMC4519280 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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An Integrative Approach for Mapping Differentially Expressed Genes and Network Components Using Novel Parameters to Elucidate Key Regulatory Genes in Colorectal Cancer.

Sehgal Manika M Gupta Rajinder R Moussa Ahmed A Singh Tiratha Raj TR

PloS one 20150729 7

For examining the intricate biological processes concerned with colorectal cancer (CRC), a systems biology approach integrating several biological components and other influencing factors is essential to understand. We performed a comprehensive system level analysis for CRC which assisted in unravelling crucial network components and many regulatory elements through a coordinated view. Using this integrative approach, the perceptive of complexity hidden in a biological phenomenon is extensively ...[more]

PMID: 26222778

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Project description:Flower development is a vital developmental process in the life cycle of woody perennials, especially fruit trees. Herein, we used transcriptomic, proteomic, and hormone analyses to investigate the key candidate genes/proteins in loquat (Eriobotrya japonica) at the stages of flower bud differentiation (FBD), floral bud elongation (FBE), and floral anthesis (FA). Comparative transcriptome analysis showed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways of hormone signal transduction and starch and sucrose metabolism. Importantly, the DEGs of hormone signal transduction were significantly involved in the signaling pathways of auxin, gibberellins (GAs), cytokinin, ethylene, abscisic acid (ABA), jasmonic acid, and salicylic acid. Meanwhile, key floral integrator genes FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and floral meristem identity genes SQUAMOSA PROMOTER BINDING LIKE (SPL), LEAFY (LFY), APETALA1 (AP1), and AP2 were significantly upregulated at the FBD stage. However, key floral organ identity genes AGAMOUS (AG), AP3, and PISTILLATA (PI) were significantly upregulated at the stages of FBE and FA. Furthermore, transcription factors (TFs) such as bHLH (basic helix-loop-helix), NAC (no apical meristem (NAM), Arabidopsis transcription activation factor (ATAF1/2) and cup-shaped cotyledon (CUC2)), MYB_related (myeloblastosis_related), ERF (ethylene response factor), and C2H2 (cysteine-2/histidine-2) were also significantly differentially expressed. Accordingly, comparative proteomic analysis of differentially accumulated proteins (DAPs) and combined enrichment of DEGs and DAPs showed that starch and sucrose metabolism was also significantly enriched. Concentrations of GA3 and zeatin were high before the FA stage, but ABA concentration remained high at the FA stage. Our results provide abundant sequence resources for clarifying the underlying mechanisms of the flower development in loquat.

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Dataset Information

An Integrative Approach for Mapping Differentially Expressed Genes and Network Components Using Novel Parameters to Elucidate Key Regulatory Genes in Colorectal Cancer.

Publications

An Integrative Approach for Mapping Differentially Expressed Genes and Network Components Using Novel Parameters to Elucidate Key Regulatory Genes in Colorectal Cancer.

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