Gradient descent optimization in gene regulatory pathways
Mouli Das1, Subhasis Mukhopadhyay, Rajat K De
1Machine Intelligence Unit, Indian Statistical Institute, Kolkata, India.
Plos One
|September 15, 2010
Summary
A new method identifies optimal gene regulatory pathways using structural equations. This approach successfully validates causal genes and discovers novel findings in systems biology for applications in medicine and molecular biology.
Area of Science:
- Systems Biology
- Genomics
- Bioinformatics
Background:
- Gene Regulatory Networks (GRNs) are crucial for understanding cellular function.
- Elucidating GRN architecture and dynamics is key in systems biology.
- GRNs offer insights into pathways with applications in medicine and drug discovery.
Purpose of the Study:
- To introduce a novel method for identifying optimal gene regulatory pathways.
- To utilize structural equations for modeling gene regulatory networks.
- To infer causal genes and generate hypotheses on regulatory mechanisms.
Main Methods:
- Developed a method using structural equations to model GRNs.
- Generated reaction flow data and formulated constraints with weighting coefficients.
- Optimized an objective function to derive gene regulatory pathways.
Main Results:
- Successfully tested the method on ten existing gene regulatory networks.
- Demonstrated favorable comparison with existing extreme pathway analysis.
- Validated pathways revealed a combination of known and novel biological findings.
Conclusions:
- The method accurately identifies causal genes and outputs experimentally verified pathways.
- Optimal regulatory pathways were derived for all considered networks.
- The method's biological significance, applicability, and usefulness in genetic engineering were discussed.
Related Concept Videos
01:23Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
02:24Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
02:24Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
02:05Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
02:05Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
02:02Cis-regulatory Sequences
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...