Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model

Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with...

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Main Authors: Johansson, A., Løset, M., Mundal, S., Johnson, M., Freed, K., Fenstad, M., Moses, Eric, Austgulen, R., Blangero, J.
Format: Journal Article
Published: 2011
Online Access:http://hdl.handle.net/20.500.11937/46976
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author Johansson, A.
Løset, M.
Mundal, S.
Johnson, M.
Freed, K.
Fenstad, M.
Moses, Eric
Austgulen, R.
Blangero, J.
author_facet Johansson, A.
Løset, M.
Mundal, S.
Johnson, M.
Freed, K.
Fenstad, M.
Moses, Eric
Austgulen, R.
Blangero, J.
author_sort Johansson, A.
building Curtin Institutional Repository
collection Online Access
description Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with alterations in the observed correlational patterns among sets of genes. Here we use partial correlation networks aiming to compare the transcriptional co-regulation for 222 genes that are differentially expressed in decidual tissues between preeclampsia (PE) cases and non-PE controls. Partial correlation coefficients (PCCs) have been calculated in cases (N = 37) and controls (N = 58) separately. For all PCCs, we tested if they were significant non-zero in the cases and controls separately. In addition, to examine if a given PCC is different between the cases and controls, we tested if the difference between two PCCs were significant non-zero. In the group with PE cases, only five PCCs were significant (FDR p value = 0.05), of which none were significantly different from the PCCs in the controls. However, in the controls we identified a total of 56 statistically significant PCCs (FDR p value = 0.05), of which 31 were also significantly different (FDR p value = 0.05) from the PCCs in the PE cases. The identified partial correlation networks included genes that are potentially relevant for developing PE, including both known susceptibility genes (EGFL7, HES1) and novel candidate genes (CFH, NADSYN1, DBP, FIGLA). Our results might suggest that disturbed interactions, or higher order relationships between these genes play an important role in developing the disease.
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spelling curtin-20.500.11937-469762018-03-29T09:06:49Z Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model Johansson, A. Løset, M. Mundal, S. Johnson, M. Freed, K. Fenstad, M. Moses, Eric Austgulen, R. Blangero, J. Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with alterations in the observed correlational patterns among sets of genes. Here we use partial correlation networks aiming to compare the transcriptional co-regulation for 222 genes that are differentially expressed in decidual tissues between preeclampsia (PE) cases and non-PE controls. Partial correlation coefficients (PCCs) have been calculated in cases (N = 37) and controls (N = 58) separately. For all PCCs, we tested if they were significant non-zero in the cases and controls separately. In addition, to examine if a given PCC is different between the cases and controls, we tested if the difference between two PCCs were significant non-zero. In the group with PE cases, only five PCCs were significant (FDR p value = 0.05), of which none were significantly different from the PCCs in the controls. However, in the controls we identified a total of 56 statistically significant PCCs (FDR p value = 0.05), of which 31 were also significantly different (FDR p value = 0.05) from the PCCs in the PE cases. The identified partial correlation networks included genes that are potentially relevant for developing PE, including both known susceptibility genes (EGFL7, HES1) and novel candidate genes (CFH, NADSYN1, DBP, FIGLA). Our results might suggest that disturbed interactions, or higher order relationships between these genes play an important role in developing the disease. 2011 Journal Article http://hdl.handle.net/20.500.11937/46976 10.1007/s00439-010-0893-5 restricted
spellingShingle Johansson, A.
Løset, M.
Mundal, S.
Johnson, M.
Freed, K.
Fenstad, M.
Moses, Eric
Austgulen, R.
Blangero, J.
Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model
title Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model
title_full Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model
title_fullStr Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model
title_full_unstemmed Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model
title_short Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model
title_sort partial correlation network analyses to detect altered gene interactions in human disease: using preeclampsia as a model
url http://hdl.handle.net/20.500.11937/46976