Disentangling non-specific and condition-specific transcriptomic responses: A framework from heat stress in yeast

Area of Science:

• Molecular Biology
• Systems Biology
• Genomics

Background:

• Distinguishing general stress responses from context-specific ones is crucial in biology.
• Bulk transcriptomic data integrates signals from heterogeneous cell populations (viable, injured, non-culturable).

Purpose of the Study:

• To develop an integrative transcriptomic framework to differentiate recurrent from condition-specific transcriptional responses.
• To analyze population-level transcriptomic data from Saccharomyces cerevisiae under different heat conditions.

Main Methods:

• Integrated 13 public and 2 in-house transcriptomic datasets from yeast.
• Applied co-expression network analysis, functional enrichment, and promoter motif discovery.
• Focused on population-level responses, not individual cells.

Main Results:

• Identified gene modules for recurrent non-specific stress responses and condition-specific responses to gradual heating.
• Heat ramp induced a broader, structured transcriptional program linked to survival, unlike heat shock.
• Observed differential responses in ribosome biogenesis, RNA processing, mitochondrial function, and proteostasis.

Conclusions:

• Proposed conceptual models for transcriptional organization under heat ramp versus heat shock, dependent on heating kinetics.
• The framework is broadly applicable for analyzing stressed populations in various biological systems.
• Stress-responsive gene clusters showed limited overlap with evolutionarily young genes.