Research Article
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Year 2025, Volume: 54 Issue: 4, 1518 - 1532, 29.08.2025
https://doi.org/10.15672/hujms.1679033

Abstract

Project Number

2021.KB.FEN.038

References

  • [1] M. Ackermann and K. Strimmer. A general modular framework for gene set enrichment analysis. BMC Bioinform. 10, 120, 2009.
  • [2] I.J. Broce, L. Stein, E. Jones and T. Kwan. C9orf72 gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types. Front. Neurosci. 18, 1258996, 2024.
  • [3] J.B. Brown. Classifiers and their metrics quantified. Mol. Inform. 37, 1700127, 2018.
  • [4] Q. Chen, R. Liu, X. Wang and H. Chen. Identification and analysis of spinal cord injury subtypes using weighted gene co-expression network analysis. Ann. Transl. Med. 9, 466, 2021.
  • [5] D. Chicco and G. Jurman. The Matthews correlation coefficient (MCC) should replace the ROC AUC as the standard metric for assessing binary classification. BioData Min. 16, 4, 2023.
  • [6] R Core Team et al., R: A language and environment for statistical computing, R Found. Stat. Comput., Vienna, 2013.
  • [7] D.J. Cummins and C.W. Andrews. Iteratively reweighted partial least squares: a performance analysis by Monte Carlo simulation. J. Chemom. 9, 489507, 1995.
  • [8] S. Datta. E xploring relationships in gene expressions: a partial least squares approach. Gene Expr. 9, 249, 2018.
  • [9] Y. Di, D. Chen, W. Yu and L. Yan. Bladder cancer stage-associated hub genes revealed by WGCNA co-expression network analysis. Hereditas 156, 111, 2019.
  • [10] A.S. Feltrin, P.R. Castro, L.F. Silva and R. Costa. Assessment of complementarity of WGCNA and NERI results for identification of modules associated to schizophrenia spectrum disorders. PLoS One 14, e0210431, 2019.
  • [11] E. Galán-Vásquez and E. Perez-Rueda. Identification of modules with similar gene regulation and metabolic functions based on co-expression data. Front. Mol. Biosci. 6, 139, 2019.
  • [12] A. Ghazalpour, B. Bennett, S. Plaisier and J. Chen. Integrating genetic and network analysis to characterize genes related to mouse weight. PLoS Genet. 2, e130, 2006.
  • [13] D.J. Guo, R. Lin and Y. Li. Identification of breast cancer prognostic modules via differential module selection based on weighted gene co-expression network analysis. BioSystems. 199, 104317, 2021.
  • [14] M. Hubert and S. Verboven. Robust methods for partial least squares regression. J. Chemom. 17, 537-549, 2003.
  • [15] S. Langfelder and S. Horvath. Fast R functions for robust correlations and hierarchical clustering. J. Stat. Softw. 46, 117, 2012.
  • [16] S. Langfelder and S. Horvath. WGCNA: an R package for weighted correlation network analysis. BMC Bioinform. 9, 113, 2008.
  • [17] B. Liebmann, P. Filzmoser and K. Varmuza. Robust and classical PLS regression compared. J. Chemom. 24, 111120, 2010.
  • [18] W. Li, Y. Zhang, L. Zhang and Q. Wang. Weighted gene co-expression network analysis to identify key modules and hub genes associated with atrial fibrillation. Int. J. Mol. Med. 45, 401416, 2020.
  • [19] S. Pan, Y. Lin, X. Liu and L. Wang. A comprehensive weighted gene co-expression network analysis uncovers potential targets in diabetic kidney disease. J. Transl. Intern. Med. 10, 359368, 2023.
  • [20] Y. Peng, X. Chen, Q. Zhang and D. Liu. Identification of immune-related biomarkers in adrenocortical carcinoma: immune-related biomarkers for ACC. Int. Immunopharmacol. 88, 106930, 2020.
  • [21] V. Pihur, S. Datta and S. Datta. Reconstruction of genetic association networks from microarray data: a partial least squares approach. Bioinformatics 24, 561568, 2008.
  • [22] E. Polat, The effects of different weight functions on partial robust m-regression performance: a simulation study. Comms. in Stats. - Sim. and Comput. 49:4, 1089- 1104, 2020.
  • [23] S. Serneels, K. Suykens, B. De Moor and S. Van Huffel. Partial robust M-regression. Chemom. Intell. Lab. Syst. 79, 5564, 2005.
  • [24] T. Van Den Bulcke, K. Van Leemput, B. Naudts and P. Van Remortel. SynTReN: a generator of synthetic gene expression data for design and analysis of structure learning algorithms. BMC Bioinform. 7, 112, 2006.
  • [25] F. Wang, H. Miao, S. Zhang, X. Hu, Y. Chu, W. Yang and J. Chen. Weighted gene co-expression network analysis reveals hub genes regulating response to salt stress in peanut. BMC Plant Biol. 24, 425, 2024.
  • [26] B. Wang, X. Li, Y. Zheng and R. Zhang. Research on a weighted gene co-expression network analysis method for mining pathogenic genes in thyroid cancer. PLoS One 17, e0272403, 2022.
  • [27] S. Wold, M. Sjöström and L. Eriksson. PLS-regression: a basic tool of chemometrics. Chemom. Intell. Lab. Syst. 58, 109130, 2001.
  • [28] C.H. Zheng, Y. Li, L. Wang and W. Zhang. Gene differential coexpression analysis based on biweight correlation and maximum clique. BMC Bioinform. 15, 17, 2014.
  • [29] B. Zhang and S. Horvath. A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol. 4, 129, 2005.

Robust gene co-expression networks via partial robust M regression

Year 2025, Volume: 54 Issue: 4, 1518 - 1532, 29.08.2025
https://doi.org/10.15672/hujms.1679033

Abstract

Gene expression data provide valuable information on the regulation and interactions of thousands of genes. However, constructing robust gene co-expression networks in the presence of outliers remains an open challenge. We propose a partial robust M regression based-method for building ene co-expression networks, which downweights extreme observations instead of discarding them. This preserves critical biological information while safeguarding the overall network structure from distortion. Through comprehensive simulations on the syntren300 dataset - including various outlier distributions (e.g. N(0, 5), N(1, 5), N(100, 10) and t(2)) and contamination levels up to 30\%, the partial robust M regression-based approach outperforms widely used methods (weighted gene co-expression network analysis, bi-weighted midcorrelation and partial least squares regression-based connectivity) in terms of precision, F1 and Matthews correlation coefficient. Real-data analysis of mouse liver gene expression further validates the stability and biological relevance of partial robust M regression-based gene co-expression networks, as it accurately identifies functionally enriched genes even under data contamination. These findings underscore the potential of partial robust M regression-based network construction to enhance reliability and uncover novel insights in high-dimensional genomic studies, offering a robust alternative to traditional correlation-based or partial least squares regression-based methods.

Supporting Institution

The first author is supported by the Department of Scientific Research Projects (BAP Project No: 2021.KB.FEN.038)

Project Number

2021.KB.FEN.038

References

  • [1] M. Ackermann and K. Strimmer. A general modular framework for gene set enrichment analysis. BMC Bioinform. 10, 120, 2009.
  • [2] I.J. Broce, L. Stein, E. Jones and T. Kwan. C9orf72 gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types. Front. Neurosci. 18, 1258996, 2024.
  • [3] J.B. Brown. Classifiers and their metrics quantified. Mol. Inform. 37, 1700127, 2018.
  • [4] Q. Chen, R. Liu, X. Wang and H. Chen. Identification and analysis of spinal cord injury subtypes using weighted gene co-expression network analysis. Ann. Transl. Med. 9, 466, 2021.
  • [5] D. Chicco and G. Jurman. The Matthews correlation coefficient (MCC) should replace the ROC AUC as the standard metric for assessing binary classification. BioData Min. 16, 4, 2023.
  • [6] R Core Team et al., R: A language and environment for statistical computing, R Found. Stat. Comput., Vienna, 2013.
  • [7] D.J. Cummins and C.W. Andrews. Iteratively reweighted partial least squares: a performance analysis by Monte Carlo simulation. J. Chemom. 9, 489507, 1995.
  • [8] S. Datta. E xploring relationships in gene expressions: a partial least squares approach. Gene Expr. 9, 249, 2018.
  • [9] Y. Di, D. Chen, W. Yu and L. Yan. Bladder cancer stage-associated hub genes revealed by WGCNA co-expression network analysis. Hereditas 156, 111, 2019.
  • [10] A.S. Feltrin, P.R. Castro, L.F. Silva and R. Costa. Assessment of complementarity of WGCNA and NERI results for identification of modules associated to schizophrenia spectrum disorders. PLoS One 14, e0210431, 2019.
  • [11] E. Galán-Vásquez and E. Perez-Rueda. Identification of modules with similar gene regulation and metabolic functions based on co-expression data. Front. Mol. Biosci. 6, 139, 2019.
  • [12] A. Ghazalpour, B. Bennett, S. Plaisier and J. Chen. Integrating genetic and network analysis to characterize genes related to mouse weight. PLoS Genet. 2, e130, 2006.
  • [13] D.J. Guo, R. Lin and Y. Li. Identification of breast cancer prognostic modules via differential module selection based on weighted gene co-expression network analysis. BioSystems. 199, 104317, 2021.
  • [14] M. Hubert and S. Verboven. Robust methods for partial least squares regression. J. Chemom. 17, 537-549, 2003.
  • [15] S. Langfelder and S. Horvath. Fast R functions for robust correlations and hierarchical clustering. J. Stat. Softw. 46, 117, 2012.
  • [16] S. Langfelder and S. Horvath. WGCNA: an R package for weighted correlation network analysis. BMC Bioinform. 9, 113, 2008.
  • [17] B. Liebmann, P. Filzmoser and K. Varmuza. Robust and classical PLS regression compared. J. Chemom. 24, 111120, 2010.
  • [18] W. Li, Y. Zhang, L. Zhang and Q. Wang. Weighted gene co-expression network analysis to identify key modules and hub genes associated with atrial fibrillation. Int. J. Mol. Med. 45, 401416, 2020.
  • [19] S. Pan, Y. Lin, X. Liu and L. Wang. A comprehensive weighted gene co-expression network analysis uncovers potential targets in diabetic kidney disease. J. Transl. Intern. Med. 10, 359368, 2023.
  • [20] Y. Peng, X. Chen, Q. Zhang and D. Liu. Identification of immune-related biomarkers in adrenocortical carcinoma: immune-related biomarkers for ACC. Int. Immunopharmacol. 88, 106930, 2020.
  • [21] V. Pihur, S. Datta and S. Datta. Reconstruction of genetic association networks from microarray data: a partial least squares approach. Bioinformatics 24, 561568, 2008.
  • [22] E. Polat, The effects of different weight functions on partial robust m-regression performance: a simulation study. Comms. in Stats. - Sim. and Comput. 49:4, 1089- 1104, 2020.
  • [23] S. Serneels, K. Suykens, B. De Moor and S. Van Huffel. Partial robust M-regression. Chemom. Intell. Lab. Syst. 79, 5564, 2005.
  • [24] T. Van Den Bulcke, K. Van Leemput, B. Naudts and P. Van Remortel. SynTReN: a generator of synthetic gene expression data for design and analysis of structure learning algorithms. BMC Bioinform. 7, 112, 2006.
  • [25] F. Wang, H. Miao, S. Zhang, X. Hu, Y. Chu, W. Yang and J. Chen. Weighted gene co-expression network analysis reveals hub genes regulating response to salt stress in peanut. BMC Plant Biol. 24, 425, 2024.
  • [26] B. Wang, X. Li, Y. Zheng and R. Zhang. Research on a weighted gene co-expression network analysis method for mining pathogenic genes in thyroid cancer. PLoS One 17, e0272403, 2022.
  • [27] S. Wold, M. Sjöström and L. Eriksson. PLS-regression: a basic tool of chemometrics. Chemom. Intell. Lab. Syst. 58, 109130, 2001.
  • [28] C.H. Zheng, Y. Li, L. Wang and W. Zhang. Gene differential coexpression analysis based on biweight correlation and maximum clique. BMC Bioinform. 15, 17, 2014.
  • [29] B. Zhang and S. Horvath. A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol. 4, 129, 2005.
There are 29 citations in total.

Details

Primary Language English
Subjects Bioinformatics
Journal Section Statistics
Authors

Ayça Ölmez 0000-0002-7715-0280

Aylin Alın 0000-0002-2977-331X

Project Number 2021.KB.FEN.038
Early Pub Date July 21, 2025
Publication Date August 29, 2025
Submission Date April 18, 2025
Acceptance Date June 21, 2025
Published in Issue Year 2025 Volume: 54 Issue: 4

Cite

APA Ölmez, A., & Alın, A. (2025). Robust gene co-expression networks via partial robust M regression. Hacettepe Journal of Mathematics and Statistics, 54(4), 1518-1532. https://doi.org/10.15672/hujms.1679033
AMA Ölmez A, Alın A. Robust gene co-expression networks via partial robust M regression. Hacettepe Journal of Mathematics and Statistics. August 2025;54(4):1518-1532. doi:10.15672/hujms.1679033
Chicago Ölmez, Ayça, and Aylin Alın. “Robust Gene Co-Expression Networks via Partial Robust M Regression”. Hacettepe Journal of Mathematics and Statistics 54, no. 4 (August 2025): 1518-32. https://doi.org/10.15672/hujms.1679033.
EndNote Ölmez A, Alın A (August 1, 2025) Robust gene co-expression networks via partial robust M regression. Hacettepe Journal of Mathematics and Statistics 54 4 1518–1532.
IEEE A. Ölmez and A. Alın, “Robust gene co-expression networks via partial robust M regression”, Hacettepe Journal of Mathematics and Statistics, vol. 54, no. 4, pp. 1518–1532, 2025, doi: 10.15672/hujms.1679033.
ISNAD Ölmez, Ayça - Alın, Aylin. “Robust Gene Co-Expression Networks via Partial Robust M Regression”. Hacettepe Journal of Mathematics and Statistics 54/4 (August2025), 1518-1532. https://doi.org/10.15672/hujms.1679033.
JAMA Ölmez A, Alın A. Robust gene co-expression networks via partial robust M regression. Hacettepe Journal of Mathematics and Statistics. 2025;54:1518–1532.
MLA Ölmez, Ayça and Aylin Alın. “Robust Gene Co-Expression Networks via Partial Robust M Regression”. Hacettepe Journal of Mathematics and Statistics, vol. 54, no. 4, 2025, pp. 1518-32, doi:10.15672/hujms.1679033.
Vancouver Ölmez A, Alın A. Robust gene co-expression networks via partial robust M regression. Hacettepe Journal of Mathematics and Statistics. 2025;54(4):1518-32.