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

Sehgal M, Gupta R, Moussa A, Singh TR - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Waknaghat, Solan, H.P. 173234, India.

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.

No MeSH data available.


Related in: MedlinePlus

Functional enrichment and annotation analyses.The 631 differentially expressed genes were subjected to manual curation and annotation analyses for their involvement in diverse biological pathways, molecular functions and cellular components.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4519280&req=5

pone.0133901.g004: Functional enrichment and annotation analyses.The 631 differentially expressed genes were subjected to manual curation and annotation analyses for their involvement in diverse biological pathways, molecular functions and cellular components.

Mentions: The majority of identified TFs belonged to zinc-coordinating class and hormone-nuclear receptor family of transcriptional regulatory system. Hepatocyte nuclear factor 4 (hnf4), nuclear receptor subfamily 2 group F member 1 (nr2f1) and down-regulator of transcription 1 (dr1) are the most recurrent TFs regulating genes in early CRC dataset and are the members of same class as well as family of TFs. All these TFs either bind directly or in the form of a complex to control the rate of transcription. This kind of information is primarily required to understand the gene regulation in a comprehensive manner. It is anticipated that for the regulation of genes involved in CRC, manipulation of regulatory region of genes specifically for the identified TFs such as hnf4, nr2f1, dr1 and their classes could provide biological insight to experimental biologists and geneticists. Further, an attempt was made to manually curate and annotate the genes for their biological roles, functions, cellular components and their implication in diverse complex biological pathways. Out of 631 differentially expressed genes, functional enrichment for 509 genes was aggravated. Maximum genes had their roles in biological regulation, protein binding and were present at membranes of the cell (Fig 4). This particular section of the manuscript provides an insight to diverse mechanisms and pathways elucidated by the regulation of genes involved in CRC pathway.


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

Sehgal M, Gupta R, Moussa A, Singh TR - PLoS ONE (2015)

Functional enrichment and annotation analyses.The 631 differentially expressed genes were subjected to manual curation and annotation analyses for their involvement in diverse biological pathways, molecular functions and cellular components.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519280&req=5

pone.0133901.g004: Functional enrichment and annotation analyses.The 631 differentially expressed genes were subjected to manual curation and annotation analyses for their involvement in diverse biological pathways, molecular functions and cellular components.
Mentions: The majority of identified TFs belonged to zinc-coordinating class and hormone-nuclear receptor family of transcriptional regulatory system. Hepatocyte nuclear factor 4 (hnf4), nuclear receptor subfamily 2 group F member 1 (nr2f1) and down-regulator of transcription 1 (dr1) are the most recurrent TFs regulating genes in early CRC dataset and are the members of same class as well as family of TFs. All these TFs either bind directly or in the form of a complex to control the rate of transcription. This kind of information is primarily required to understand the gene regulation in a comprehensive manner. It is anticipated that for the regulation of genes involved in CRC, manipulation of regulatory region of genes specifically for the identified TFs such as hnf4, nr2f1, dr1 and their classes could provide biological insight to experimental biologists and geneticists. Further, an attempt was made to manually curate and annotate the genes for their biological roles, functions, cellular components and their implication in diverse complex biological pathways. Out of 631 differentially expressed genes, functional enrichment for 509 genes was aggravated. Maximum genes had their roles in biological regulation, protein binding and were present at membranes of the cell (Fig 4). This particular section of the manuscript provides an insight to diverse mechanisms and pathways elucidated by the regulation of genes involved in CRC pathway.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Waknaghat, Solan, H.P. 173234, India.

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.

No MeSH data available.


Related in: MedlinePlus