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Nonlinear gene cluster analysis with labeling for microarray gene expression data in organ development.

Ehler M, Rajapakse VN, Zeeberg BR, Brooks BP, Brown J, Czaja W, Bonner RF - BMC Proc (2011)

Bottom Line: Our nonlinear methods created clusters of genes that mapped onto more specific biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates than conventional linear cluster algorithms.The combination of LCM of embryonic organs, gene expression microarrays, and nonlinear dimension reduction with labeling is a potentially useful approach to extract subtle spatial and temporal co-variations within the gene regulatory networks that specify mammalian organogenesis and organ function.Our results motivate further analysis of nonlinear dimension reduction with labeling within other microarray data sets from LCM dissected tissues or other cell specific samples to determine the more general utility of our method for uncovering more specific biological functional relationships.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Medical Biophysics, Bethesda MD 20892, USA. ehlermar@mail.nih.gov.

ABSTRACT

Background: The gene networks underlying closure of the optic fissure during vertebrate eye development are not well-understood. We use a novel clustering method based on nonlinear dimension reduction with data labeling to analyze microarray data from laser capture microdissected (LCM) cells at the site and developmental stages (days 10.5 to 12.5) of optic fissure closure.

Results: Our nonlinear methods created clusters of genes that mapped onto more specific biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates than conventional linear cluster algorithms. Our new methods build on the advantages of LCM to isolate pure phenotypic populations within complex tissues in order to identify systems biology relationships among critical gene products expressed at lower copy number.

Conclusions: The combination of LCM of embryonic organs, gene expression microarrays, and nonlinear dimension reduction with labeling is a potentially useful approach to extract subtle spatial and temporal co-variations within the gene regulatory networks that specify mammalian organogenesis and organ function. Our results motivate further analysis of nonlinear dimension reduction with labeling within other microarray data sets from LCM dissected tissues or other cell specific samples to determine the more general utility of our method for uncovering more specific biological functional relationships.

No MeSH data available.


outliers Outliers that LE+k-means captures into a separate cluster, the associated Affymetrix probes are 1427262_at, 1427263_at, 1436936_s_at. All three probes are associated to XIST, a gene that is transcribed and spliced but does not appear to encode a protein. XIST inactivation is known to be an early developmental process in mammalian females.
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Figure 8: outliers Outliers that LE+k-means captures into a separate cluster, the associated Affymetrix probes are 1427262_at, 1427263_at, 1436936_s_at. All three probes are associated to XIST, a gene that is transcribed and spliced but does not appear to encode a protein. XIST inactivation is known to be an early developmental process in mammalian females.

Mentions: We have identified a 50 per cent larger gene cluster than with hierarchical clustering in [8] whose spatio-temporal gene expressions significantly correlate with nlz2, a gene which when previously inhibited in zebrafish induced coloboma. The latter cluster is associated with 210 Affymetrix probes corresponding to 169 genes, nlz2 was among them. See Figures 6 and 7 for gene expression profiles and its set of enriched functional categories. GoMiner assigns the functional category of ‘gene silencing’, indicating the repressive influence of nlz2 and co-varying genes. Previous biological studies have shown nlz2 gene product to repress gene transcription of a number of genes regulated hindbrain development possibly as part of a transcription factor complex consistent with its H2N2 zinc finger domain and its binding site for histone deacetylase. Consistent with this hypothesis, we also identify an additional cluster that varies inversely with the primary ‘nlz2 cluster’ gene silencing, suggestive of the previously documented role of nlz2 in suppression of gene transcription, cf. Figure 8.


Nonlinear gene cluster analysis with labeling for microarray gene expression data in organ development.

Ehler M, Rajapakse VN, Zeeberg BR, Brooks BP, Brown J, Czaja W, Bonner RF - BMC Proc (2011)

outliers Outliers that LE+k-means captures into a separate cluster, the associated Affymetrix probes are 1427262_at, 1427263_at, 1436936_s_at. All three probes are associated to XIST, a gene that is transcribed and spliced but does not appear to encode a protein. XIST inactivation is known to be an early developmental process in mammalian females.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3090761&req=5

Figure 8: outliers Outliers that LE+k-means captures into a separate cluster, the associated Affymetrix probes are 1427262_at, 1427263_at, 1436936_s_at. All three probes are associated to XIST, a gene that is transcribed and spliced but does not appear to encode a protein. XIST inactivation is known to be an early developmental process in mammalian females.
Mentions: We have identified a 50 per cent larger gene cluster than with hierarchical clustering in [8] whose spatio-temporal gene expressions significantly correlate with nlz2, a gene which when previously inhibited in zebrafish induced coloboma. The latter cluster is associated with 210 Affymetrix probes corresponding to 169 genes, nlz2 was among them. See Figures 6 and 7 for gene expression profiles and its set of enriched functional categories. GoMiner assigns the functional category of ‘gene silencing’, indicating the repressive influence of nlz2 and co-varying genes. Previous biological studies have shown nlz2 gene product to repress gene transcription of a number of genes regulated hindbrain development possibly as part of a transcription factor complex consistent with its H2N2 zinc finger domain and its binding site for histone deacetylase. Consistent with this hypothesis, we also identify an additional cluster that varies inversely with the primary ‘nlz2 cluster’ gene silencing, suggestive of the previously documented role of nlz2 in suppression of gene transcription, cf. Figure 8.

Bottom Line: Our nonlinear methods created clusters of genes that mapped onto more specific biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates than conventional linear cluster algorithms.The combination of LCM of embryonic organs, gene expression microarrays, and nonlinear dimension reduction with labeling is a potentially useful approach to extract subtle spatial and temporal co-variations within the gene regulatory networks that specify mammalian organogenesis and organ function.Our results motivate further analysis of nonlinear dimension reduction with labeling within other microarray data sets from LCM dissected tissues or other cell specific samples to determine the more general utility of our method for uncovering more specific biological functional relationships.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Medical Biophysics, Bethesda MD 20892, USA. ehlermar@mail.nih.gov.

ABSTRACT

Background: The gene networks underlying closure of the optic fissure during vertebrate eye development are not well-understood. We use a novel clustering method based on nonlinear dimension reduction with data labeling to analyze microarray data from laser capture microdissected (LCM) cells at the site and developmental stages (days 10.5 to 12.5) of optic fissure closure.

Results: Our nonlinear methods created clusters of genes that mapped onto more specific biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates than conventional linear cluster algorithms. Our new methods build on the advantages of LCM to isolate pure phenotypic populations within complex tissues in order to identify systems biology relationships among critical gene products expressed at lower copy number.

Conclusions: The combination of LCM of embryonic organs, gene expression microarrays, and nonlinear dimension reduction with labeling is a potentially useful approach to extract subtle spatial and temporal co-variations within the gene regulatory networks that specify mammalian organogenesis and organ function. Our results motivate further analysis of nonlinear dimension reduction with labeling within other microarray data sets from LCM dissected tissues or other cell specific samples to determine the more general utility of our method for uncovering more specific biological functional relationships.

No MeSH data available.