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Related Concept Videos

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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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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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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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...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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COFFEE: Consensus Single Cell-Type Specific Inference for Gene Regulatory Networks.

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  • 1Integrative Life Sciences, Virginia Commonwealth University, Richmond, VA 23284.

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Summary

Consensus algorithms like COFFEE improve gene regulatory network (GRN) inference for single-cell RNA sequencing (scRNA-seq) data. This wisdom of crowds approach enhances accuracy by integrating multiple GRN inference methods.

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Area of Science:

  • Computational biology
  • Genomics
  • Systems biology

Background:

  • Gene regulatory networks (GRNs) are fundamental to biological processes.
  • Inferring GRNs from single-cell RNA sequencing (scRNA-seq) data is challenging.
  • Previous consensus methods showed promise for bulk RNA-seq data.

Approach:

  • Developed COFFEE (COnsensus single cell-type speciFic inFerence for gEnE regulatory networks), a Borda voting-based consensus algorithm.
  • Integrated information from 10 established GRN inference methods.
  • Evaluated performance on synthetic, curated, and experimental scRNA-seq datasets.

Key Points:

  • COFFEE demonstrated improved performance compared to baseline GRN inference methods.
  • A modified COFFEE version enhanced newer cell-type specific GRN inference techniques.
  • Consensus-based approaches remain valuable for scRNA-seq GRN inference.

Conclusions:

  • Consensus algorithms, like COFFEE, offer a robust strategy for GRN inference in scRNA-seq data.
  • The wisdom of crowds approach, adapted for single-cell data, significantly improves network reconstruction.
  • COFFEE provides a valuable tool for deciphering regulatory mechanisms at the single-cell level.