Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain

Tomita, Hiroaki; Vawter, Marquis P.; Walsh, David M.; Evans, Simon J.; Choudary, Prabhakara V.; Li, Jun; Overman, Kevin M.; Atz, Mary E.; Myers, Richard M.; Jones, Edward G.
Biological Psychiatry. 2004; 55(4):346-352.


There are major concerns that specific agonal conditions, including coma and hypoxia, might affect ribonucleic acid (RNA) integrity in postmortem brain studies. We report that agonal factors significantly affect RNA integrity and have a major impact on gene expression profiles in microarrays. In contrast to agonal factors, gender, age, and postmortem factors have less effect on gene expression profiles. The Average Correlation Index is proposed as a method for evaluating RNA integrity on the basis of similarity of microarray profiles. Reducing the variance due to agonal factors is critical in investigating small but validated gene expression differences in messenger RNA levels between psychiatric patients and control subjects.