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Related Concept Videos

RNA Splicing01:32

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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SEPARATING THE CAUSES AND CONSEQUENCES IN DISEASE TRANSCRIPTOME.

Yong Fuga Li1, Fuxiao Xin, Russ B Altman

  • 1Department of Bioengineering, Stanford University, USA2Stanford Genome Technology Center, Stanford University, USA.

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Summary
This summary is machine-generated.

Identifying complex disease causes is challenging. Our diseaseExPatho approach integrates transcriptome, regulome, and genome-wide association study (GWAS) data to pinpoint causal gene modules, even when not differentially expressed.

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Area of Science:

  • Genomics
  • Systems Biology
  • Computational Biology

Background:

  • Complex diseases have multifactorial causes and heterogeneous phenotypes, complicating research.
  • Transcriptome profiling offers insights but struggles to disentangle disease causes from consequences.
  • Genome-wide association studies (GWAS) identify genetic factors but lack comprehensive pathogenetic views.

Purpose of the Study:

  • To develop and validate diseaseExPatho, a novel computational approach for separating causal and consequential signals in disease transcriptomes.
  • To integrate transcriptome data, regulome knowledge, and GWAS results for improved disease mechanism discovery.

Main Methods:

  • diseaseExPatho computationally deconvolutes gene expression data into modules.
  • Modules are hierarchically ranked using a novel regulome-based algorithm.
  • Potential causal gene modules are labeled by correlating with GWAS data.

Main Results:

  • Putative causal modules were identified that were not necessarily differentially expressed.
  • Strongly differentially expressed modules often lacked enrichment for top GWAS variations.
  • Regulome-based module ranking consistently prioritized causal modules across six diseases.

Conclusions:

  • diseaseExPatho effectively separates disease causes and consequences within transcriptomes.
  • The approach can prioritize causal pathways in complex diseases, with or without GWAS data.
  • This method aids in understanding disease pathogenesis for both common and rare conditions.