Limits...
Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.

Rojas-Peña ML, Olivares-Navarrete R, Hyzy S, Arafat D, Schwartz Z, Boyan BD, Williams J, Gibson G - J Genomics (2014)

Bottom Line: Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures.Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity.Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.

ABSTRACT
Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

No MeSH data available.


Related in: MedlinePlus

Two-way hierarchical clustering of craniosynostosis samples. The heat map represents the overall similarity of profiles from low (blue) to high (red) indicating two major clusters of expression profiles corresponding to 8025 transcripts in 31 individuals. The Normal cluster also shows a suggestion of differentiation between long bone and skull-derived osteoblast cultures. Within craniosynostosis groups, there are three clusters (A, B, and C). There is no significant correlation between site of synostosis (indicated at the left) and overall clustering of profiles.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4150121&req=5

Figure 2: Two-way hierarchical clustering of craniosynostosis samples. The heat map represents the overall similarity of profiles from low (blue) to high (red) indicating two major clusters of expression profiles corresponding to 8025 transcripts in 31 individuals. The Normal cluster also shows a suggestion of differentiation between long bone and skull-derived osteoblast cultures. Within craniosynostosis groups, there are three clusters (A, B, and C). There is no significant correlation between site of synostosis (indicated at the left) and overall clustering of profiles.

Mentions: Clustering of samples according to overall similarity (Fig. 2) confirmed these results. Seven of the of the normal samples form a distinct group along with two of the craniosynostosis samples, while the remaining 21 craniosynostosis samples were no more likely to cluster according to region than expected by chance. However, it is noteworthy that the first cluster of mostly normal samples does appear to separate into two sub-groups of skull or long bone samples, suggesting a subtle difference between of these two sources of osteoblasts.


Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.

Rojas-Peña ML, Olivares-Navarrete R, Hyzy S, Arafat D, Schwartz Z, Boyan BD, Williams J, Gibson G - J Genomics (2014)

Two-way hierarchical clustering of craniosynostosis samples. The heat map represents the overall similarity of profiles from low (blue) to high (red) indicating two major clusters of expression profiles corresponding to 8025 transcripts in 31 individuals. The Normal cluster also shows a suggestion of differentiation between long bone and skull-derived osteoblast cultures. Within craniosynostosis groups, there are three clusters (A, B, and C). There is no significant correlation between site of synostosis (indicated at the left) and overall clustering of profiles.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4150121&req=5

Figure 2: Two-way hierarchical clustering of craniosynostosis samples. The heat map represents the overall similarity of profiles from low (blue) to high (red) indicating two major clusters of expression profiles corresponding to 8025 transcripts in 31 individuals. The Normal cluster also shows a suggestion of differentiation between long bone and skull-derived osteoblast cultures. Within craniosynostosis groups, there are three clusters (A, B, and C). There is no significant correlation between site of synostosis (indicated at the left) and overall clustering of profiles.
Mentions: Clustering of samples according to overall similarity (Fig. 2) confirmed these results. Seven of the of the normal samples form a distinct group along with two of the craniosynostosis samples, while the remaining 21 craniosynostosis samples were no more likely to cluster according to region than expected by chance. However, it is noteworthy that the first cluster of mostly normal samples does appear to separate into two sub-groups of skull or long bone samples, suggesting a subtle difference between of these two sources of osteoblasts.

Bottom Line: Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures.Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity.Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.

ABSTRACT
Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

No MeSH data available.


Related in: MedlinePlus