Abstract
The integration of disparate data types provides a more complete picture of complex biological systems. Here we combine small-volume metabolomic and transcriptomic platforms to determine subtle chemical changes and to link metabolites and genes to biochemical pathways. Capillary electrophoresis-mass spectrometry (CE-MS) and whole-genome gene expression arrays, aided by integrative pathway analysis, were utilized to survey metabolomic/transcriptomic hippocampal neurochemistry. We measured changes in individual hippocampi from the mast cell mutant mouse strain, C57BL/6 KitW-sh/W-sh. These mice have a naturally occurring mutation in the white spotting locus that causes reduced c-Kit receptor expression and an inability of mast cells to differentiate from their hematopoietic progenitors. Compared with their littermates, the mast cell-deficient mice have profound deficits in spatial learning, memory, and neurogenesis. A total of 18 distinct metabolites were identified in the hippocampus that discriminated between the C57BL/6 Kit W-sh/W-sh and control mice. The combined analysis of metabolite and gene expression changes revealed a number of altered pathways. Importantly, results from both platforms indicated that multiple pathways are impacted, including amino acid metabolism, increasing the confidence in each approach. Because the CE-MS and expression profiling are both amenable to small-volume analysis, this integrated analysis is applicable to a range of volume-limited biological systems.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3136-3143 |
| Number of pages | 8 |
| Journal | Analytical chemistry |
| Volume | 85 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 19 2013 |
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ASJC Scopus subject areas
- Analytical Chemistry
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Combining small-volume metabolomic and transcriptomic approaches for assessing brain chemistry. / Knolhoff, Ann M.; Nautiyal, Katherine M.; Nemes, Peter; Kalachikov, Sergey; Morozova, Irina; Silver, Rae; Sweedler, Jonathan V.
In: Analytical chemistry, Vol. 85, No. 6, 19.03.2013, p. 3136-3143.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combining small-volume metabolomic and transcriptomic approaches for assessing brain chemistry
AU - Knolhoff, Ann M.
AU - Nautiyal, Katherine M.
AU - Nemes, Peter
AU - Kalachikov, Sergey
AU - Morozova, Irina
AU - Silver, Rae
AU - Sweedler, Jonathan V.
PY - 2013/3/19
Y1 - 2013/3/19
N2 - The integration of disparate data types provides a more complete picture of complex biological systems. Here we combine small-volume metabolomic and transcriptomic platforms to determine subtle chemical changes and to link metabolites and genes to biochemical pathways. Capillary electrophoresis-mass spectrometry (CE-MS) and whole-genome gene expression arrays, aided by integrative pathway analysis, were utilized to survey metabolomic/transcriptomic hippocampal neurochemistry. We measured changes in individual hippocampi from the mast cell mutant mouse strain, C57BL/6 KitW-sh/W-sh. These mice have a naturally occurring mutation in the white spotting locus that causes reduced c-Kit receptor expression and an inability of mast cells to differentiate from their hematopoietic progenitors. Compared with their littermates, the mast cell-deficient mice have profound deficits in spatial learning, memory, and neurogenesis. A total of 18 distinct metabolites were identified in the hippocampus that discriminated between the C57BL/6 Kit W-sh/W-sh and control mice. The combined analysis of metabolite and gene expression changes revealed a number of altered pathways. Importantly, results from both platforms indicated that multiple pathways are impacted, including amino acid metabolism, increasing the confidence in each approach. Because the CE-MS and expression profiling are both amenable to small-volume analysis, this integrated analysis is applicable to a range of volume-limited biological systems.
AB - The integration of disparate data types provides a more complete picture of complex biological systems. Here we combine small-volume metabolomic and transcriptomic platforms to determine subtle chemical changes and to link metabolites and genes to biochemical pathways. Capillary electrophoresis-mass spectrometry (CE-MS) and whole-genome gene expression arrays, aided by integrative pathway analysis, were utilized to survey metabolomic/transcriptomic hippocampal neurochemistry. We measured changes in individual hippocampi from the mast cell mutant mouse strain, C57BL/6 KitW-sh/W-sh. These mice have a naturally occurring mutation in the white spotting locus that causes reduced c-Kit receptor expression and an inability of mast cells to differentiate from their hematopoietic progenitors. Compared with their littermates, the mast cell-deficient mice have profound deficits in spatial learning, memory, and neurogenesis. A total of 18 distinct metabolites were identified in the hippocampus that discriminated between the C57BL/6 Kit W-sh/W-sh and control mice. The combined analysis of metabolite and gene expression changes revealed a number of altered pathways. Importantly, results from both platforms indicated that multiple pathways are impacted, including amino acid metabolism, increasing the confidence in each approach. Because the CE-MS and expression profiling are both amenable to small-volume analysis, this integrated analysis is applicable to a range of volume-limited biological systems.
UR - http://www.scopus.com/inward/record.url?scp=84875477914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875477914&partnerID=8YFLogxK
U2 - 10.1021/ac3032959
DO - 10.1021/ac3032959
M3 - Article
C2 - 23409944
AN - SCOPUS:84875477914
VL - 85
SP - 3136
EP - 3143
JO - Analytical Chemistry
JF - Analytical Chemistry
SN - 0003-2700
IS - 6
ER -