STREAM

STREAM models transcriptional regulation using a thermodynamic framework to simulate how transcription factors (TFs) and transcription factor binding sites (TFBSs) influence gene transcription rates.

Key Features:

• Modeling and Visualization: Integrates TF concentrations, TFBS locations, and measured transcription rates to model and visualize regulatory interactions across a gene's regulatory DNA region.
• Parameter Optimization: Optimizes model parameters from input data to fit observed transcription rates.
• Predictive Capabilities: Predicts transcription rates under varied conditions, including different tissue types, TF knockouts or additional TFs, and mutated or missing TFBSs.
• Validation of Regulatory Mechanisms: Evaluates whether specified sets of TFs can reproduce observed regulatory effects on target genes.

Scientific Applications:

• Regulatory grammar discovery: Enables identification of combinatorial TF effects and regulatory grammar governing gene expression.
• Genetics and molecular biology: Supports analyses of gene regulation mechanisms relevant to genetics and molecular biology.
• Systems biology: Provides quantitative models for systems-level studies of gene regulatory networks.
• Synthetic biology and biotechnology: Informs design by predicting transcriptional responses to engineered changes in TFs or TFBSs.
• Disease research: Aids investigation of regulatory mechanisms with potential relevance to disease and therapeutic strategies.

Methodology:

Applies a thermodynamic approach using thermodynamic equations to compute equilibrium states of TF–DNA interactions from inputs of TF concentrations, TFBSs, and transcription rates, and performs parameter optimization to fit models and generate transcription rate predictions.