Regulatory grammar in human promoters uncovered by MPRA-based deep learning - Nature

TSS Selection Criteria

Background

The selection of relevant Transcription Start Sites (TSSs) is a crucial step in understanding gene expression and regulation. In this study, we followed established procedures to identify active TSSs that meet specific criteria.

Methodology

As described previously, the selection of TSSs was based on the GENCODE database. This comprehensive resource provides a wealth of information on human genes, including their genomic coordinates, transcription start sites, and expression patterns.

In addition to the standard criteria used in previous studies, we introduced an additional requirement for TSSs:

  • They must be defined as active in at least one cell type.

This more stringent criterion aimed to increase the specificity of our results, ensuring that only truly active TSSs were included in our analysis.

TSS Selection Process

The selection process involved several steps:

  1. GENCODE Database: We utilized the GENCODE database to identify all defined TSSs for human genes.
  2. Filtering Criteria: We applied filtering criteria to narrow down the list of potential TSSs, ensuring that only those with active annotation were considered.
  3. Cell Type Validation: To further validate our results, we checked which cell types had been reported to express the selected TSSs.

Implications

The selection of relevant TSSs has significant implications for understanding gene expression and regulation:

  • Gene Expression Regulation: The identification of active TSSs can provide insights into how genes are regulated in different cell types.
  • Cellular Differentiation: By analyzing TSS activity across various cell types, researchers can gain a better understanding of the mechanisms underlying cellular differentiation.

Future Research Directions

The selection of relevant TSSs is an essential step in understanding gene expression and regulation. Future research directions may include:

  • Integrating TSS Data with Other Genomic Resources: Combining TSS data with other genomic resources, such as ChIP-seq or RNA-seq data, can provide a more comprehensive understanding of gene regulation.
  • Analyzing TSS Activity in Different Diseases: By examining TSS activity in different diseases, researchers can identify potential therapeutic targets and gain insights into the mechanisms underlying disease progression.

Conclusion

The selection of relevant TSSs is a critical step in understanding gene expression and regulation. By following established procedures and introducing additional filtering criteria, we increased the specificity of our results and provided a more accurate representation of active TSSs. Future research directions will focus on integrating TSS data with other genomic resources and analyzing TSS activity in different diseases.

References

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