TY  - INPR
A1  - Lobentanzer, Sebastian
A1  - Hanin, Geula
A1  - Klein, Jochen
A1  - Soreq, Hermona
T1  - Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder
T2  - bioRxiv
N2  - RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male- and female-originated cell lines, and connectomics of transcription factor- and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies disease-affected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72588
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-725881
IS  - 600932
ER  -