Toward Best Practices for Imaging Transcriptomics of the Human Brain.

Area of Science:

• Neuroscience
• Genomics
• Bioinformatics

Background:

• Modern brainwide transcriptional atlases offer insights into brain organization.
• Integrating transcriptomic data with neuroimaging requires careful methodological consideration for valid inferences.

Purpose of the Study:

• To review methodological choices in imaging transcriptomic analyses.
• To facilitate standardized and reproducible approaches in this emerging field.
• To identify sources of variability and mitigate false positive results.

Main Methods:

• Review of methodological choices in 3 phases: transcriptional atlas processing, relating transcriptomics to neuroimaging phenotypes, and gene enrichment analysis.
• Identification of key choices affecting findings and strategies for mitigating spurious results.
• Overview of open-source toolboxes for best-practice procedures.

Main Results:

• Methodological variability significantly impacts imaging transcriptomic analyses.
• Specific choices in data processing and analysis influence the identification of molecular correlates.
• Gene enrichment analysis is crucial for evaluating functional implications.

Conclusions:

• Standardized and reproducible methods are essential for robust imaging transcriptomic studies.
• Careful consideration of methodological choices is needed to ensure valid inferences.
• Open-source tools can support best practices in the field.