Study of gene function based on spatial co-expression in a high-resolution mouse brain atlas.
BACKGROUND
The Allen Brain Atlas (ABA) project systematically profiles three-dimensional high-resolution gene expression in postnatal mouse brains for thousands of genes. By unveiling gene behaviors at both the cellular and molecular levels, ABA is becoming a unique and comprehensive neuroscience data source for decoding enigmatic biological processes in the brain. Given the unprecedented volume and complexity of the in situ hybridization image data, data mining in this area is extremely challenging. Currently, the ABA database mainly serves as an online reference for visual inspection of individual genes; the underlying rich information of this large data set is yet to be explored by novel computational tools. In this proof-of-concept study, we studied the hypothesis that genes sharing similar three-dimensional expression profiles in the mouse brain are likely to share similar biological functions.


RESULTS
In order to address the pattern comparison challenge when analyzing the ABA database, we developed a robust image filtering method, dubbed histogram-row-column (HRC) algorithm. We demonstrated how the HRC algorithm offers the sensitivity of identifying a manageable number of gene pairs based on automatic pattern searching from an original large brain image collection. This tool enables us to quickly identify genes of similar in situ hybridization patterns in a semi-automatic fashion and consequently allows us to discover several gene expression patterns with expression neighborhoods containing genes of similar functional categories.


CONCLUSIONS
Given a query brain image, HRC is a fully automated algorithm that is able to quickly mine vast number of brain images and identify a manageable subset of genes that potentially shares similar spatial co-distribution patterns for further visual inspection. A three-dimensional in situ hybridization pattern, if statistically significant, could serve as a fingerprint of certain gene function. Databases such as ABA provide valuable data source for characterizing brain-related gene functions when armed with powerful image querying tools like HRC.
Liu
Zheng
Z
Department of Computer Science, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA. zliu@cs.ucr.edu
Yan
S Frank
SF
Walker
John R
JR
Zwingman
Theresa A
TA
Jiang
Tao
T
Li
Jing
J
Zhou
Yingyao
Y
D000262:Adenylyl Cyclases / Q000235:genetics / Q000502:physiology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000378:metabolism; D030541:Databases, Genetic; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D020869:Gene Expression Profiling; D005796:Genes / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; C493215:Slc6a3 protein, mouse; C061368:cyclic AMP-regulated phosphoprotein ARPP-21; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D004298:Dopamine