Analysis of gene activity helps classify brain disorders 2023

The research of Yashar Zeighami at McGill University in Canada offers a novel method for characterizing brain disorders. The study, which was published in the open-access journal PLOS Biology, suggests that comparing transcriptomes (the map of activity for all genes in the genome) associated with various brain diseases will help us understand the underlying mechanisms of the diseases and why some are comorbid.

Numerous brain disorders have complex genetic and environmental risk factors, which makes classification difficult. Moreover, the symptoms of numerous brain disorders overlap. Parkinson’s disease and dementia with Lewy bodies, for instance, are neurodegenerative conditions characterized by tremors and rigidity of the muscles, as well as certain cognitive and behavioral symptoms.

The method can uncover novel connections between diseases, which may have implications for clinical therapy options.

Misdiagnosis is common in this and similar circumstances, and it can have significant consequences for patient care. Another strategy is to classify brain diseases according to gene activity. This investigation examined disease transcriptomes, which are collections of RNA transcripts from diseased brain regions, for forty distinct brain disorders.

Based on where disease-risk genes were active in the brain and which cell types, the researchers found that this system could classify brain diseases into five primary categories. In addition to confirming known relationships between diseases, disease transcriptome analysis was able to identify relationships between diseases that were previously unknown.

For instance, language development disorders, obsessive-compulsive disorder, and temporal lobe epilepsy were all placed in group 3, indicating that despite their very distinct symptoms, their respective genes are active in the same brain regions and cell types. Neurodegenerative, movement-related, and psychiatric brain diseases are the most difficult to diagnose due to the overlap of symptoms that alter over time. Thus, a transcriptome is an additional diagnostic instrument that could be used to make more precise early diagnoses.

Zeighami adds, “Analysis of the transcription patterns of human brain disease risk genes reveals signature expression patterns across brain anatomy. These can be employed to compare and aggregate diseases, yielding associations that frequently deviate from conventional phenotypic classification.”