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Annotation

Colantuoni C, Lipska BK, Ye T, Hyde TM, Tao R, Leek JT, Colantuoni EA, Elkahloun AG, Herman MM, Weinberger DR, Kleinman JE. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature . 2011 Oct 27 ; 478(7370):519-23. PubMed Abstract

Comments on Paper and Primary News
Primary News: The Life and Times of the Human Brain Transcriptome

Comment by:  Karoly Mirnics, SRF Advisor
Submitted 31 October 2011 Posted 31 October 2011

Well done! Finally, some systematic transcriptome profiling of the human brain on a large scale. If we are ever going to crack neurodevelopmental disorders, such datasets will be absolutely critical. Exon-level transcriptome and associated genotyping data, brain regions, gender differences, developmental trajectories—this manuscript has it all. However, this is only a start, a catalogue of molecular events that begs to be explored. We see the complexity contained within the dataset, and it is simply mind-boggling. How do we make sense out of all this? Which changes are characteristic of interneurons, and which trajectories are projection neuron derived? How are the changes related to maturation of layers or various diseases? The mining of this dataset is far from over. It will be interesting to see what a WGCNA type of analysis will uncover in this proverbial gold mine. We need new ideas, we need new bioinformatic tools to look at this.

In addition, based on the presented data, we need to form precise, testable hypotheses. And then will come the hardest part—we...  Read more


View all comments by Karoly Mirnics

Primary News: The Life and Times of the Human Brain Transcriptome

Comment by:  Paul Harrison
Submitted 2 November 2011 Posted 3 November 2011
  I recommend this paper

The Nature papers by Colantuoni et al. (2011) and Kang et al. (2011) are landmark studies, not only because of the wealth of data about the human brain transcriptome across the lifespan that they contain, but as a resource for other researchers to dip into or mine as they wish. Both papers represent the culmination of extensive research programs, and are based ultimately on the crucial, sensitive, and often unappreciated task of collecting a sufficient number of well-characterized brains (Deep-Soboslay et al., 2011). In turn (as noted by Karoly Mirnics in his comment), they also attest to the importance of having funding schemes which permit this kind of ambitious, long-term, large-scale—and expensive—research. The papers set a new gold standard for human brain studies in terms of size and scope. They also illustrate the renaissance of postmortem brain research, and provide confirmation (if any was needed) that human brain diseases need direct study of human brains—including normative analyses across the...  Read more


View all comments by Paul Harrison

Primary News: The Life and Times of the Human Brain Transcriptome

Comment by:  Marquis Vawter
Submitted 9 November 2011 Posted 10 November 2011
  I recommend this paper

Just a passing comment. I believe the study by Kang et al. shows an interesting change in gene expression of the MIR137, which was strongly implicated by GWAS.

Both of these papers are extremely useful, and welcomed for the study of eQTLs in human brain.

View all comments by Marquis Vawter


Comment by:  Takanori Hashimoto
Submitted 29 November 2011 Posted 29 November 2011

I am interested in the database on significant associations between SNPs and gene expression levels in the prefrontal cortex (PFC) because we might be able to understand how genetic variance associated with schizophrenia contributes to PFC dysfunction in schizophrenia. The database will allow us to identify functional genes whose expression levels in the PFC are controlled by schizophrenia-associated SNPs. If they are expressed and have specific roles in the mature PFC, we can assess their significance in the pathophysiology by evaluating expression changes in schizophrenia using postmortem brains. It is also possible that some of these genes have already been reported to exhibit altered expression levels in the PFC of schizophrenia subjects, contributing to specific aspects of PFC dysfunctions. Therefore, this database appears to be important for further understanding of the pathogenetic and pathophysiological mechanisms of schizophrenia and the development of efficient treatments for PFC dysfunction in schizophrenia.

However, to my disappointment, the access is...  Read more


View all comments by Takanori Hashimoto

Primary News: The Life and Times of the Human Brain Transcriptome

Comment by:  Yasue Horiuchi, Shin-ichi KanoAkira Sawa (SRF Advisor)Ashley Wilson
Submitted 1 December 2011 Posted 1 December 2011

These two new papers show the spatial and temporal regulation of gene expression in the human brain across various ages. Although it is not novel to observe various patterns of gene expression during human brain development, systematic bioinformatics approaches using such enormous sample sizes will lead us to a new level of understanding the complexity of the transcriptome during development.

Both groups showed that age is a very strong contributor to global differences in gene expression compared to other variables such as sex, ethnicity, and inter-individual variation. Thus, transcriptional differences and changes are most pronounced during early development, gradually slowing through infancy, adolescence, and into adulthood—each stage having a clear transcriptional profile. Kang et al. further showed that gene expression is also spatially regulated. Furthermore, they found many co-expressed gene groups that were spatially and temporally regulated. They also reported sex-biased gene expression.

Our group, like many other laboratories, is trying to approach...  Read more


View all comments by Yasue Horiuchi
View all comments by Shin-ichi Kano
View all comments by Akira Sawa
View all comments by Ashley Wilson
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