Dataset Information

Large scale comparison of global gene expression patterns in human and mouse.

ABSTRACT: BACKGROUND:It is widely accepted that orthologous genes between species are conserved at the sequence level and perform similar functions in different organisms. However, the level of conservation of gene expression patterns of the orthologous genes in different species has been unclear. To address the issue, we compared gene expression of orthologous genes based on 2,557 human and 1,267 mouse samples with high quality gene expression data, selected from experiments stored in the public microarray repository ArrayExpress. RESULTS:In a principal component analysis (PCA) of combined data from human and mouse samples merged on orthologous probesets, samples largely form distinctive clusters based on their tissue sources when projected onto the top principal components. The most prominent groups are the nervous system, muscle/heart tissues, liver and cell lines. Despite the great differences in sample characteristics and experiment conditions, the overall patterns of these prominent clusters are strikingly similar for human and mouse. We further analyzed data for each tissue separately and found that the most variable genes in each tissue are highly enriched with human-mouse tissue-specific orthologs and the least variable genes in each tissue are enriched with human-mouse housekeeping orthologs. CONCLUSIONS:The results indicate that the global patterns of tissue-specific expression of orthologous genes are conserved in human and mouse. The expression of groups of orthologous genes co-varies in the two species, both for the most variable genes and the most ubiquitously expressed genes.

SUBMITTER: Zheng-Bradley X

PROVIDER: S-EPMC3046484 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Large scale comparison of global gene expression patterns in human and mouse.

Zheng-Bradley Xiangqun X Rung Johan J Parkinson Helen H Brazma Alvis A

Genome biology 20101223 12

<h4>Background</h4>It is widely accepted that orthologous genes between species are conserved at the sequence level and perform similar functions in different organisms. However, the level of conservation of gene expression patterns of the orthologous genes in different species has been unclear. To address the issue, we compared gene expression of orthologous genes based on 2,557 human and 1,267 mouse samples with high quality gene expression data, selected from experiments stored in the public ...[more]

PMID: 21182765

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Project description:Depression is a complex mental health disorder that is difficult to study. A wide range of animal models exist and for many of these data on large-scale gene expression patterns in the CNS are available. The goal of this study was to evaluate how well animal models match human depression by evaluating congruence and discordance of large-scale gene expression patterns in the CNS between almost 300 animal models and a portrait of human depression created from male and female datasets. Multiple approaches were used, including a hypergeometric based scoring system that rewards common gene expression patterns (e.g., up-up or down-down in both model and human depression), but penalizes opposing gene expression patterns. RRHO heat maps, Uniform Manifold Approximation Plot (UMAP), and machine learning were used to evaluate matching of models to depression. The top ranked model was a histone deacetylase (HDAC2) conditional knockout in forebrain neurons. Also highly ranked were various models for Alzheimer's, including APPsa knock-in (2nd overall), APP knockout, and an APP/PS1 humanized double mutant. Other top models were the mitochondrial gene HTRA2 knockout (that is lethal in adulthood), a modified acetylcholinesterase, a Huntington's disease model, and the CRTC1 knockout. Over 30 stress related models were evaluated and while some matched highly with depression, others did not. In most of the top models, a consistent dysregulation of MAP kinase pathway was identified and the genes NR4A1, BDNF, ARC, EGR2, and PDE7B were consistently downregulated as in humans with depression. Separate male and female portraits of depression were also evaluated to identify potential sex specific depression matches with models. Individual human depression datasets were also evaluated to allow for comparisons across the same brain regions. Heatmap, UMAP, and machine learning results supported the hypergeometric ranking findings. Together, this study provides new insights into how large-scale gene expression patterns may be similarly dysregulated in some animals models and humans with depression that may provide new avenues for understanding and treating depression.

Dataset Information

Large scale comparison of global gene expression patterns in human and mouse.

Publications

Large scale comparison of global gene expression patterns in human and mouse.

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