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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
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The genome refers to all of the genetic material in an organism. It can range from a few million base pairs in microbial cells to several billion base pairs in many eukaryotic organisms. Genome assembly refers to the process of taking the DNA sequencing data and putting it all back together in a correct order to create a close representation of the original genome. This is followed by the identification of functional elements on the newly assembled genome, a process called genome annotation.
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Augmenting microarray data with literature-based knowledge to enhance gene regulatory network inference.

Guocai Chen1, Michael J Cairelli1, Halil Kilicoglu1

  • 1Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland, United States of America.

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Summary
This summary is machine-generated.

This study integrates literature-derived gene interactions with microarray data to build more accurate gene regulatory networks. The novel approach enhances biological modeling by reducing reliance on random gene selection.

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Area of Science:

  • Systems Biology
  • Computational Biology
  • Bioinformatics

Background:

  • Gene regulatory networks are vital for understanding cellular mechanisms.
  • Current computational models often use random gene selection, limiting accuracy.
  • Prior knowledge integration in gene network inference is typically restricted.

Purpose of the Study:

  • To investigate the impact of using semantic relations from literature to augment microarray data for gene network inference.
  • To develop a more accurate model of cellular behavior by incorporating literature-based gene interactions.
  • To eliminate the need for random gene selection in non-exhaustive network inference approaches.

Main Methods:

  • Augmenting microarray data with semantic relations extracted from scientific literature.
  • Employing a genetic algorithm to optimize interaction strengths.
  • Utilizing an artificial neural network for fitness evaluation.
  • Testing the model on invasive ductile carcinoma of the breast and yeast datasets.

Main Results:

  • The developed model demonstrated significantly better fitness compared to state-of-the-art methods relying on random gene selection.
  • The inferred gene regulatory networks contained both known and novel relationships, with significant validation of p53 pathway interactions.
  • The methodology showed superior performance on both human cancer and yeast datasets.

Conclusions:

  • Combining literature-derived semantic relations with microarray analysis effectively generates contribution-weighted gene regulatory networks.
  • This integrated approach offers a significant advancement in understanding complex cellular interactions and molecular physiology.
  • The method provides a more accurate and biologically relevant representation of gene regulatory processes.