Brain Imaging Transcriptomics

Question 1

Define

Imaging transcriptomics

Answer 1

Mapping brain imaging phenotypes to spatial variation in gene expression

Correlating what we see in brain images with the underlying molecular activities at the gene expression level.

Question 2

Explain

Spatial variation in disease vulnerability

Answer 2

• Brain diseases target specific areas of the brain
• The sequence in which areas are affected determines the clinical expression of the disease

Question 3

Define

MRI

Answer 3

• Magnetic Resonance Imaging
• Radiofrequency pulses are applied to measure contrasts between tissue types

Question 4

Define

PET

Answer 4

• Positron Emission Tomography
• Radioactively labeled ligands (tracers) are injected and used to estimate binding to different molecules (glucose, receptors, etc…)

Question 5

Define

MEG

Answer 5

• Magnetoencephalography
• Magnetic fields generated by ionic currents in the brain are measured at the surface and used to infer neural activity

Question 6

How was the AHBA created?

Answer 6

• Six post-mortem brains (ages 24-57)
• Whole brain microarray
• Over 20,000 genes from 3,702 tissue samples
• 3D MRI coordinates for all probes

Question 7

What were the initial findings after studying genomic patterning in the brain?

Answer 7

1. High spatial variation (follows distribution of specialized cell types)
2. Proximal probes have similar transcriptomic profiles (high spatial autocorrelation, neighboring regions exhibit similar gene expression patterns)
3. Conserved across individuals

Question 8

What are the questions to be asked when studying

Regional expression

Answer 8

How do genes co-vary with brain phenotypes, e.g. disease atrophy, task activation, myelination, synapse density, metabolism, etc.?

Question 9

What are the questions to be asked when studying

Correlated gene expression

Answer 9

Are areas with similar transcriptomic profiles more likely to be physically connected and to communicate with each other?

Question 10

What are the questions to be asked when studying

Gene coexpression

Answer 10

Are genes with similar spatial distributions involved in similar functions?

Question 11

Define

Abagen

Answer 11

• Python toolbox for downloading and pre-processing the AHBA
• Works w/ volumetric and surface analysis

Question 12

How are parameters ranked by importance?

Answer 12

1. Normalization parameters
2. Parameters related to how tissue samples are matched to brain regions
3. Parameters related to probe selection

Question 13

Define

Differential stability

Answer 13

• Differential stability is a correlation-based metric, used to assess the reproducibility of gene expression patterns.
• A gene with a higher DS (differential stability score) will tend to exhibit the same or similar differential expression relationships across brain structures.