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Comparing genomic expression patterns across species identifies shared transcriptional profile in aging
Abstract
We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.
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“GBA approaches are also widely used to identify new potential disease genes if a substantial proportion of the genes within a module are associated with a particular disease [26, 121–126] (Figure 1).”
From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [125]
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“Deregulation of mitochondrial function is a common feature in multiple aspects of aging.”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [6]
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“Taken together these findings suggest of a causal role of mitochondrial dysfunction in the aging process and a central role for mitochondrial adaptation in the mechanism of aging retardation by CR”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [6]
In the citing paper
“Foremost among these and pertinent to this review are genes involved in mitochondrial energy metabolism.”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [6]
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Metadata
- Authors
- McCarroll, S. A., Murphy, C. T., Zou, S., Pletcher, S. D., Chin, C.-S., Jan, Y. N., Kenyon, C., Bargmann, C. I., & Li, H.
- Affiliations
- University of California, San Francisco (US)
- University College London (GB)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Li, Hao
- ORCID
- Venue
- Nature Genetics
- Published
- 2004-01-18
- Volume
- 36
- Issue
- 2
- Pages
- 197-204
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2118852675
- Cited by
- 454
- References
- 51
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 28 · 2020: 15 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 12 · 2012: 29
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Consorzio Interuniversitario Biotecnologie
- National Institute on Deafness and Other Communication Disorders
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- gene expression comparison, orthologs, aging, gene expression signatures, Gene Ontology, Caenorhabditis elegans, Drosophila melanogaster, mitochondrial metabolism, DNA repair, larval development, embryonic development, gametogenesis, mRNA degradation
- MeSH terms
- Age Factors, Aging, Animals, Drosophila melanogaster, Gene Expression Regulation, Humans, Phylogeny, Saccharomyces cerevisiae, Time Factors, Caenorhabditis elegans, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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