Humphrey Lab

Genetics of Neurodegeneration

A study of RNA splicing and protein expression in the living human brain


Journal article


B. Kopell, Deepak A Kaji, Lora E. Liharska, Eric Vornholt, Anina N Lund, Alice Hashemi, Ryan C Thompson, Jessica S. Johnson, Nicole Bussola, Esther Cheng, You Jeong Park, Punit Shah, Weiping Ma, R. Searfoss, Gregory M. Miller, N. M. Chand, Jack Humphrey, Lillian Wilkins, Kimia Ziafat, Hannah Silk, Lisa M Linares, Brendan Sullivan, Claudia Feng, Vanessa Cohen, Prashant Kota, E. Moya, M. Rieder, Girish N. Nadkarni, Michael S. Breen, Joseph Scarpa, N. Narain, Pei Wang, Michael A. Kiebish, Eric E. Schadt, Noam D. Beckmann, Alexander W. Charney
PLoS ONE, 2025

Semantic Scholar DOI PubMedCentral PubMed
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APA   Click to copy
Kopell, B., Kaji, D. A., Liharska, L. E., Vornholt, E., Lund, A. N., Hashemi, A., … Charney, A. W. (2025). A study of RNA splicing and protein expression in the living human brain. PLoS ONE.


Chicago/Turabian   Click to copy
Kopell, B., Deepak A Kaji, Lora E. Liharska, Eric Vornholt, Anina N Lund, Alice Hashemi, Ryan C Thompson, et al. “A Study of RNA Splicing and Protein Expression in the Living Human Brain.” PLoS ONE (2025).


MLA   Click to copy
Kopell, B., et al. “A Study of RNA Splicing and Protein Expression in the Living Human Brain.” PLoS ONE, 2025.


BibTeX   Click to copy

@article{b2025a,
  title = {A study of RNA splicing and protein expression in the living human brain},
  year = {2025},
  journal = {PLoS ONE},
  author = {Kopell, B. and Kaji, Deepak A and Liharska, Lora E. and Vornholt, Eric and Lund, Anina N and Hashemi, Alice and Thompson, Ryan C and Johnson, Jessica S. and Bussola, Nicole and Cheng, Esther and Park, You Jeong and Shah, Punit and Ma, Weiping and Searfoss, R. and Miller, Gregory M. and Chand, N. M. and Humphrey, Jack and Wilkins, Lillian and Ziafat, Kimia and Silk, Hannah and Linares, Lisa M and Sullivan, Brendan and Feng, Claudia and Cohen, Vanessa and Kota, Prashant and Moya, E. and Rieder, M. and Nadkarni, Girish N. and Breen, Michael S. and Scarpa, Joseph and Narain, N. and Wang, Pei and Kiebish, Michael A. and Schadt, Eric E. and Beckmann, Noam D. and Charney, Alexander W.}
}

Abstract

Due to the unavailability of living human brain tissue for molecular research, postmortem brain samples are currently the standard tissue source for molecular studies of the human brain. The Living Brain Project (LBP) was designed to test the assumption that the postmortem brain is an accurate molecular representation of in the living brain on multiple levels of molecular biology. Findings from previous LBP reports suggest that this assumption does not hold with respect to RNA transcript expression levels. Here, molecular differences between living and postmortem human prefrontal cortex tissues obtained for the LBP are corroborated through analyses of RNA splicing and protein expression data. Significant differences were observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, and (3) the patterns of co-expression between RNA transcripts and proteins. Taken together, this report corroborates the presence of widespread molecular differences between living and postmortem human brain tissues. These observations should be considered when designing and interpreting studies of human brain biology.


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