Large-Scale Analysis of Gene Expression and Connectivity in the Rodent Brain: Insights Through Data Integration

Overview

Journal Front Neuroinform

Specialty Neurology

Date 2011 Aug 25

PMID 21863139

Citations 25

Authors

Leon French

Powell Patrick Cheng Tan

Paul Pavlidis

Affiliations

Soon will be listed here.

Abstract

Recent research in C. elegans and the rodent has identified correlations between gene expression and connectivity. Here we extend this type of approach to examine complex patterns of gene expression in the rodent brain in the context of regional brain connectivity and differences in cellular populations. Using multiple large-scale data sets obtained from public sources, we identified two novel patterns of mouse brain gene expression showing a strong degree of anti-correlation, and relate this to multiple data modalities including macroscale connectivity. We found that these signatures are associated with differences in expression of neuronal and oligodendrocyte markers, suggesting they reflect regional differences in cellular populations. We also find that the expression level of these genes is correlated with connectivity degree, with regions expressing the neuron-enriched pattern having more incoming and outgoing connections with other regions. Our results exemplify what is possible when increasingly detailed large-scale cell- and gene-level data sets are integrated with connectivity data.

Citing Articles

Functional diversities within neurons and astrocytes in the adult rat auditory cortex revealed by single-nucleus RNA sequencing.

Gungor Aydin A, Lemenze A, Bieszczad K Sci Rep. 2024; 14(1):25314.

PMID: 39455606 PMC: 11511993. DOI: 10.1038/s41598-024-74732-7.

BrainTACO: an explorable multi-scale multi-modal brain transcriptomic and connectivity data resource.

Ganglberger F, Kargl D, Topfer M, Hernandez-Lallement J, Lawless N, Fernandez-Albert F Commun Biol. 2024; 7(1):730.

PMID: 38877144 PMC: 11178817. DOI: 10.1038/s42003-024-06355-7.

Transcriptomic and connectomic correlates of differential spatial patterning among gliomas.

Romero-Garcia R, Mandal A, Bethlehem R, Crespo-Facorro B, Hart M, Suckling J Brain. 2022; 146(3):1200-1211.

PMID: 36256589 PMC: 9976966. DOI: 10.1093/brain/awac378.

Overcoming false-positive gene-category enrichment in the analysis of spatially resolved transcriptomic brain atlas data.

Fulcher B, Arnatkeviciute A, Fornito A Nat Commun. 2021; 12(1):2669.

PMID: 33976144 PMC: 8113439. DOI: 10.1038/s41467-021-22862-1.

Uncovering Statistical Links Between Gene Expression and Structural Connectivity Patterns in the Mouse Brain.

Timonidis N, Llera A, Tiesinga P Neuroinformatics. 2021; 19(4):649-667.

PMID: 33704701 PMC: 8566442. DOI: 10.1007/s12021-021-09511-0.

References

Dong H, Swanson L, Chen L, Fanselow M, Toga A . Genomic-anatomic evidence for distinct functional domains in hippocampal field CA1. Proc Natl Acad Sci U S A. 2009; 106(28):11794-9. PMC: 2710698. DOI: 10.1073/pnas.0812608106. View

Ghandour M, Langley O, Vincendon G, Gombos G . Double labeling immunohistochemical technique provides evidence of the specificity of glial cell markers. J Histochem Cytochem. 1979; 27(12):1634-7. DOI: 10.1177/27.12.118210. View

Wheeler D, Barrett T, Benson D, Bryant S, Canese K, Chetvernin V . Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 2006; 35(Database issue):D5-12. PMC: 1781113. DOI: 10.1093/nar/gkl1031. View

Akil H, Martone M, Van Essen D . Challenges and opportunities in mining neuroscience data. Science. 2011; 331(6018):708-12. PMC: 3102049. DOI: 10.1126/science.1199305. View

Wu Y, Zhang A, Yew D . Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus. Neurochem Int. 2005; 46(7):565-74. DOI: 10.1016/j.neuint.2005.01.002. View

Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25(1):25-9. PMC: 3037419. DOI: 10.1038/75556. View

Sporns O, Tononi G, Kotter R . The human connectome: A structural description of the human brain. PLoS Comput Biol. 2005; 1(4):e42. PMC: 1239902. DOI: 10.1371/journal.pcbi.0010042. View

Rosengren L, Kjellstrand P, Aurell A, Haglid K . Irreversible effects of dichloromethane on the brain after long term exposure: a quantitative study of DNA and the glial cell marker proteins S-100 and GFA. Br J Ind Med. 1986; 43(5):291-9. PMC: 1007652. DOI: 10.1136/oem.43.5.291. View

Lein E, Hawrylycz M, Ao N, Ayres M, Bensinger A, Bernard A . Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2006; 445(7124):168-76. DOI: 10.1038/nature05453. View

10.

Wolf L, Goldberg C, Manor N, Sharan R, Ruppin E . Gene expression in the rodent brain is associated with its regional connectivity. PLoS Comput Biol. 2011; 7(5):e1002040. PMC: 3088660. DOI: 10.1371/journal.pcbi.1002040. View

11.

Ghandour M, Langley O, Labourdette G, Vincendon G, Gombos G . Specific and artefactual cellular localizations of S 100 protein: an astrocyte marker in rat cerebellum. Dev Neurosci. 1981; 4(1):66-78. DOI: 10.1159/000112742. View

12.

Biswal B, Mennes M, Zuo X, Gohel S, Kelly C, Smith S . Toward discovery science of human brain function. Proc Natl Acad Sci U S A. 2010; 107(10):4734-9. PMC: 2842060. DOI: 10.1073/pnas.0911855107. View

13.

Kotter R . Online retrieval, processing, and visualization of primate connectivity data from the CoCoMac database. Neuroinformatics. 2004; 2(2):127-44. DOI: 10.1385/NI:2:2:127. View

14.

Cahoy J, Emery B, Kaushal A, Foo L, Zamanian J, Christopherson K . A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008; 28(1):264-78. PMC: 6671143. DOI: 10.1523/JNEUROSCI.4178-07.2008. View

15.

Swanson L, Bota M . Foundational model of structural connectivity in the nervous system with a schema for wiring diagrams, connectome, and basic plan architecture. Proc Natl Acad Sci U S A. 2010; 107(48):20610-7. PMC: 2996420. DOI: 10.1073/pnas.1015128107. View

16.

Bota M, Dong H, Swanson L . Brain architecture management system. Neuroinformatics. 2005; 3(1):15-48. DOI: 10.1385/NI:3:1:015. View

17.

Harris T, Antoshechkin I, Bieri T, Blasiar D, Chan J, Chen W . WormBase: a comprehensive resource for nematode research. Nucleic Acids Res. 2009; 38(Database issue):D463-7. PMC: 2808986. DOI: 10.1093/nar/gkp952. View

18.

Kaufman A, Dror G, Meilijson I, Ruppin E . Gene expression of Caenorhabditis elegans neurons carries information on their synaptic connectivity. PLoS Comput Biol. 2006; 2(12):e167. PMC: 1676027. DOI: 10.1371/journal.pcbi.0020167. View

19.

Hawrylycz M, Baldock R, Burger A, Hashikawa T, Johnson G, Martone M . Digital atlasing and standardization in the mouse brain. PLoS Comput Biol. 2011; 7(2):e1001065. PMC: 3033370. DOI: 10.1371/journal.pcbi.1001065. View

20.

Bohland J, Bokil H, Allen C, Mitra P . The brain atlas concordance problem: quantitative comparison of anatomical parcellations. PLoS One. 2009; 4(9):e7200. PMC: 2748707. DOI: 10.1371/journal.pone.0007200. View