Limits...
Defining the gene expression signature of rhabdomyosarcoma by meta-analysis.

Romualdi C, De Pittà C, Tombolan L, Bortoluzzi S, Sartori F, Rosolen A, Lanfranchi G - BMC Genomics (2006)

Bottom Line: Our results point to a general down regulation of the energy production pathways, suggesting a hypoxic physiology for RMS cells.This gene is involved in anti-apoptotic processes when cells grow in low oxygen conditions.These new insights in the biological processes responsible of RMS growth and development demonstrate the effective advantage of the use of integrated analysis of gene expression studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: CRIBI Biotechnology Centre and Biology Department, University of Padova, Padova, Italy. chiara.romualdi@unipd.it <chiara.romualdi@unipd.it>

ABSTRACT

Background: Rhabdomyosarcoma is a highly malignant soft tissue sarcoma in childhood and arises as a consequence of regulatory disruption of the growth and differentiation pathways of myogenic precursor cells. The pathogenic pathways involved in this tumor are mostly unknown and therefore a better characterization of RMS gene expression profile would represent a considerable advance. The availability of publicly available gene expression datasets have opened up new challenges especially for the integration of data generated by different research groups and different array platforms with the purpose of obtaining new insights on the biological process investigated.

Results: In this work we performed a meta-analysis on four microarray and two SAGE datasets of gene expression data on RMS in order to evaluate the degree of agreement of the biological results obtained by these different studies and to identify common regulatory pathways that could be responsible of tumor growth. Regulatory pathways and biological processes significantly enriched has been investigated and a list of differentially meta-profiles have been identified as possible candidate of aggressiveness of RMS.

Conclusion: Our results point to a general down regulation of the energy production pathways, suggesting a hypoxic physiology for RMS cells. This result agrees with the high malignancy of RMS and with its resistance to most of the therapeutic treatments. In this context, different isoforms of the ANT gene have been consistently identified for the first time as differentially expressed in RMS. This gene is involved in anti-apoptotic processes when cells grow in low oxygen conditions. These new insights in the biological processes responsible of RMS growth and development demonstrate the effective advantage of the use of integrated analysis of gene expression studies.

Show MeSH

Related in: MedlinePlus

Frequency distribution of the mean pairwise Spearman correlation coefficient obtained from the comparison (with a jackknives procedure) of the expression profiles of probes belonging to the same Entrez Gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1636648&req=5

Figure 3: Frequency distribution of the mean pairwise Spearman correlation coefficient obtained from the comparison (with a jackknives procedure) of the expression profiles of probes belonging to the same Entrez Gene.

Mentions: All the expression datasets derived from microarray platforms show a similar level of RD (see the Methods for details) while, as expected, the SAGE dataset (composed by some 46,000 tags) has a significantly higher RD value. On the other hand, Figure 3 shows the distribution of the platform reproducibility index (RP), defined as the mean correlation of pairwise expression profiles of probes assigned to the same EG entry for each platform (see the Methods for details). We found that cDNA platforms show a distribution centered on RP value of 0.3–0.4, while Affymetrix platforms of 0.0–0.1. Probes in the Affimetrix platform are synthesized as pairs of short oligonucleotides: each couple consists of an oligonucleotide perfectly matched to the target sequence and a twin oligonucleotide mismatched at a single position. This probe configuration should give a higher specificity of probes for the identification of transcript variants and alternative splicing isoforms. On the other hand, cDNA platforms contain probes with long sequences and, even if designed on the 3' or 5' portions of transcripts, could result in less specific hybridizations with targets. Our results are in agreement with those obtained by Lee et al. where UniGene clusters were used to match the probes of platforms [19]. The variability in the expression profiles of genes belonging to the same EG entry introduces a degree of complexity in the comparison of probes across different array platforms. In this context, the introduction of meta-profiles (see the Methods section) allows us the comparison of EG entries across different studies. Then, a meta-profile is defined as the trimmed median profile of the probes annotated with the same EG and is virtually representative of that gene. After identifying EG entries common to all the six studies, statistical tests (permutational t-test for microarray data and Audic and Claverie test for SAGE data) have been performed on meta-profiles.


Defining the gene expression signature of rhabdomyosarcoma by meta-analysis.

Romualdi C, De Pittà C, Tombolan L, Bortoluzzi S, Sartori F, Rosolen A, Lanfranchi G - BMC Genomics (2006)

Frequency distribution of the mean pairwise Spearman correlation coefficient obtained from the comparison (with a jackknives procedure) of the expression profiles of probes belonging to the same Entrez Gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1636648&req=5

Figure 3: Frequency distribution of the mean pairwise Spearman correlation coefficient obtained from the comparison (with a jackknives procedure) of the expression profiles of probes belonging to the same Entrez Gene.
Mentions: All the expression datasets derived from microarray platforms show a similar level of RD (see the Methods for details) while, as expected, the SAGE dataset (composed by some 46,000 tags) has a significantly higher RD value. On the other hand, Figure 3 shows the distribution of the platform reproducibility index (RP), defined as the mean correlation of pairwise expression profiles of probes assigned to the same EG entry for each platform (see the Methods for details). We found that cDNA platforms show a distribution centered on RP value of 0.3–0.4, while Affymetrix platforms of 0.0–0.1. Probes in the Affimetrix platform are synthesized as pairs of short oligonucleotides: each couple consists of an oligonucleotide perfectly matched to the target sequence and a twin oligonucleotide mismatched at a single position. This probe configuration should give a higher specificity of probes for the identification of transcript variants and alternative splicing isoforms. On the other hand, cDNA platforms contain probes with long sequences and, even if designed on the 3' or 5' portions of transcripts, could result in less specific hybridizations with targets. Our results are in agreement with those obtained by Lee et al. where UniGene clusters were used to match the probes of platforms [19]. The variability in the expression profiles of genes belonging to the same EG entry introduces a degree of complexity in the comparison of probes across different array platforms. In this context, the introduction of meta-profiles (see the Methods section) allows us the comparison of EG entries across different studies. Then, a meta-profile is defined as the trimmed median profile of the probes annotated with the same EG and is virtually representative of that gene. After identifying EG entries common to all the six studies, statistical tests (permutational t-test for microarray data and Audic and Claverie test for SAGE data) have been performed on meta-profiles.

Bottom Line: Our results point to a general down regulation of the energy production pathways, suggesting a hypoxic physiology for RMS cells.This gene is involved in anti-apoptotic processes when cells grow in low oxygen conditions.These new insights in the biological processes responsible of RMS growth and development demonstrate the effective advantage of the use of integrated analysis of gene expression studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: CRIBI Biotechnology Centre and Biology Department, University of Padova, Padova, Italy. chiara.romualdi@unipd.it <chiara.romualdi@unipd.it>

ABSTRACT

Background: Rhabdomyosarcoma is a highly malignant soft tissue sarcoma in childhood and arises as a consequence of regulatory disruption of the growth and differentiation pathways of myogenic precursor cells. The pathogenic pathways involved in this tumor are mostly unknown and therefore a better characterization of RMS gene expression profile would represent a considerable advance. The availability of publicly available gene expression datasets have opened up new challenges especially for the integration of data generated by different research groups and different array platforms with the purpose of obtaining new insights on the biological process investigated.

Results: In this work we performed a meta-analysis on four microarray and two SAGE datasets of gene expression data on RMS in order to evaluate the degree of agreement of the biological results obtained by these different studies and to identify common regulatory pathways that could be responsible of tumor growth. Regulatory pathways and biological processes significantly enriched has been investigated and a list of differentially meta-profiles have been identified as possible candidate of aggressiveness of RMS.

Conclusion: Our results point to a general down regulation of the energy production pathways, suggesting a hypoxic physiology for RMS cells. This result agrees with the high malignancy of RMS and with its resistance to most of the therapeutic treatments. In this context, different isoforms of the ANT gene have been consistently identified for the first time as differentially expressed in RMS. This gene is involved in anti-apoptotic processes when cells grow in low oxygen conditions. These new insights in the biological processes responsible of RMS growth and development demonstrate the effective advantage of the use of integrated analysis of gene expression studies.

Show MeSH
Related in: MedlinePlus