Related Experiment Video
Updated: May 27, 2026
12:54
Real-time Analysis of Transcription Factor Binding, Transcription, Translation, and Turnover to Display Global Events During Cellular Activation
Published on: March 7, 2018
Decoding sequence determinants of gene expression in diverse cellular and disease states
Avantika Lal1, Alexander Karollus2,3,4, Laura Gunsalus2
1Biology Research | AI Development, gRED Computational Sciences, Genentech, South San Francisco, CA, USA. lal.avantika@gene.com.
Nature Methods
|May 25, 2026
Summary
Decima predicts gene expression in specific cell types using DNA sequence. This new model, trained on millions of cells, advances understanding of gene regulation and noncoding genetic variation.
Area of Science:
- Genomics
- Computational Biology
- Molecular Biology
Background:
- Sequence-to-function models predict gene expression from DNA.
- Current models lack cell type and state specificity, trained on bulk data.
- Single-cell transcriptomics offers high-resolution cellular data.
Purpose of the Study:
- To develop a model predicting cell type- and condition-specific gene expression from DNA sequence.
- To enable analysis of gene regulation at single-cell resolution.
- To interpret noncoding genetic variation effects in specific cell contexts.
Main Methods:
- Developed Decima, a novel sequence-to-function model.
- Trained Decima on over 22 million single-cell/single-nucleus RNA sequencing datasets.
- Validated Decima's ability to predict cell-type-specific gene expression for unseen genes.
Main Results:
- Decima successfully predicts cell type-specific gene expression from DNA sequence.
- Demonstrated Decima's utility in identifying cis-regulatory mechanisms driving cell-specific expression.
- Showcased Decima's capability in predicting noncoding variant effects at cell type resolution.
Conclusions:
- Decima advances sequence-to-function modeling by incorporating single-cell data.
- The model provides a powerful tool for understanding cell-type-specific gene regulation and disease mechanisms.
- Decima facilitates the design of context-specific regulatory DNA elements.
Related Concept Videos
01:36What is Gene Expression?
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...
01:42What is Gene Expression?
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
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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...
01:58Cell Specific Gene Expression
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...