Subgroup analysis of heterogeneous groups is a crucial step in the development of individualized treatment and personalized marketing strategies. Regression-based approaches are one of the main schools of subgroup analysis, a paradigm that divides predictor variables into two parts with heterogeneous and homogeneous effects and divides the sample into subgroups based on the heterogeneous effects. However, most of the existing regression-based subgroup analysis methods have two major limitations: First, they still consider the sample homogeneous within subgroups and do not fully consider individual effects; Second, the common contamination phenomenon of homogeneous effect variables is not taken into account, which will lead to large bias in the model results. To address these challenges, we propose a robust individualized subgroup analysis. We use a multidirectional separation penalty function to achieve individualized effects analysis for the heterogeneous part of the model and use γ-divergence to obtain robust estimates for the contaminated homogeneous part. We also propose an efficient alternating iterative two-step algorithm, combining coordinate descent and alternating direction method of multipliers (ADMM) techniques to implement this process. Our proposed method is further illustrated by simulation studies and analysis of a skin cutaneous melanoma dataset.
[1] Hocking T D, Joulin A, Bach F, et al. Clusterpath an algorithm for clustering using convex fusion penalties[C/OL]//Proceedings of the 28th International Conference on Machine Learning. June 28-July 2, 2011, Bellevue, Washington, USA. ICML, 2011:1.https://hal.archives-ouvertes.fr/hal-00591630.
[2] Lindsten F, Ohlsson H, Ljung L. Clustering using sum-of-norms regularization: with application to particle filter output computation[C]//2011 IEEE Statistical Signal Processing Workshop. June 28-30, 2011, Nice, France. IEEE, 2011: 201-204. DOI:10.1109/SSP.2011.5967659.
[3] Pan W, Shen X T, Liu B H. Cluster analysis: Unsupervised learning via supervised learning with a non-convex penalty[J]. Journal of Machine Learning Research, 2013, 14(1): 1865. https://pubmed.ncbi.nlm.nih.gov/24358018.
[4] Ma S J, Huang J. A concave pairwise fusion approach to subgroup analysis[J]. Journal of the American Statistical Association, 2017, 112(517): 410-423. DOI:10.1080/01621459.2016.1148039.
[5] Tang X W, Xue F, Qu A. Individualized multidirectional variable selection[J]. Journal of the American Statistical Association, 2021, 116(535): 1280-1296. DOI: 10.1080/01621459.2019.1705308.
[6] Bhalla S, Kaur H, Dhall A, et al. Prediction and analysis of skin cancer progression using genomics profiles of patients[J]. Scientific Reports, 2019, 9(1): 1-16. DOI:10.1038/s41598-019-52134-4.
[7] Basu A, Harris I R, Hjort N L, et al. Robust and efficient estimation by minimising a density power divergence[J]. Biometrika, 1998, 85(3): 549-559. DOI:10.1093/biomet/85.3.549.
[8] Fujisawa H, Eguchi S. Robust estimation in the normal mixture model[J]. Journal of Statistical Planning and Inference, 2006, 136(11): 3989-4011. DOI: 10.1016/j.jspi.2005.03.008.
[9] Ghosh A, Basu A. Robust estimation for independent non-homogeneous observations using density power divergence with applications to linear regression[J]. Electronic Journal of Statistics, 2013, 7: 2420-2456. DOI:10.1214/13-EJS847.
[10] Durio A, Isaia E D. The minimum density power divergence approach in building robust regression models[J]. Informatica, 2011, 22(1): 43-56. DOI:10.15388/Informatica.2011.313.
[11] Zang Y G, Zhao Q, Zhang Q Z, et al. Inferring gene regulatory relationships with a high-dimensional robust approach[J]. Genetic Epidemiology, 2017, 41(5): 437-454. DOI:10.1002/gepi.22047.
[12] Jones M C, Hjort N L, Harris I R, et al. A comparison of related density-based minimum divergence estimators[J]. Biometrika, 2001, 88(3): 865-873. DOI:10.1093/biomet/88.3.865.
[13] Fujisawa H, Eguchi S. Robust parameter estimation with a small bias against heavy contamination[J]. Journal of Multivariate Analysis, 2008, 99(9): 2053-2081. DOI:10.1016/j.jmva.2008.02.004.
[14] Kawashima T, Fujisawa H. Robust and sparse regression via γ-divergence[J]. Entropy, 2017, 19(11): 608. DOI:10.3390/e19110608.
[15] Hung H, Jou Z Y, Huang S Y. Robust mislabel logistic regression without modeling mislabel probabilities[J]. Biometrics, 2018, 74(1): 145-154. DOI:10.1111/biom.12726.
[16] Ren M Y, Zhang S G, Zhang Q Z. Robust high-dimensional regression for data with anomalous responses[J]. Annals of the Institute of Statistical Mathematics, 2021, 73(4): 703-736. DOI:10.1007/s10463-020-00764-1.
[17] Boyd S, Parikh N, Chu E, et al. Distributed optimization and statistical learning via the alternating direction method of multipliers[J]. Foundations and Trends in Machine Learning, 2011, 3(1):1-122. DOI:10.1561/2200000016.
[18] Smith S A, O’Meara B C. treePL: divergence time estimation using penalized likelihood for large phylogenies[J]. Bioinformatics, 2012, 28(20): 2689-2690. DOI:10.1093/bioinformatics/bts492.
[19] Mollah M N H, Eguchi S, Minami M. Robust prewhitening for ICA by minimizing β-divergence and its application to FastICA[J]. Neural Processing Letters, 2007, 25(2): 91-110. DOI:10.1007/s11063-006-9023-8.
[20] Zhang L, Wang Q, Wang L J, et al. OSskcm: an online survival analysis webserver for skin cutaneous melanoma based on 1085 transcriptomic profiles[J]. Cancer Cell International, 2020, 20: 176. DOI: 10.1186/s12935-020-01262-3.
[21] Volkovova K, Bilanicova D, Bartonova A, et al. Associations between environmental factors and incidence of cutaneous melanoma. Review[J]. Environmental Health: A Global Access Science Source, 2012, 11(Suppl 1): S12. DOI:10.1186/1476-069X-11-S1-S12.
[22] Lambert S R. Molecular profiling of cutaneous squamous cell carcinoma[D]. London, Queen Mary University of London, 2010. https://qmro.qmul.ac.uk/xmlui/handle/123456789/564.
[23] Ramazzotti D, Lal A, Wang B, et al. Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival[J]. Nature Communications, 2018, 9: 4453. DOI:10.1038/s41467-018-06921-8.
[24] Bartlam M, Yamamoto T. The structural basis for deadenylation by the CCR4-NOT complex[J]. Protein & Cell, 2010, 1(5): 443-452. DOI:10.1007/s13238-010-0060-8.
[25] Hillen L M, Geybels M S, Spassova I, et al. A digital mRNA expression signature to classify challenging spitzoid melanocytic neoplasms[J]. FEBS Open Bio, 2020, 10(7): 1326-1341. DOI:10.1002/2211-5463.12897.
[26] Sun P, Li Y, Chao X, et al. Clinical characteristics and prognostic implications of BRCA-associated tumors in males: a pan-tumor survey[J]. BMC Cancer, 2020, 20(1): 994. DOI:10.1186/s12885-020-07481-1.
[27] Miñoza J M A, Rico J A, Zamora P R F, et al. Biomarker discovery for meta-classification of melanoma metastatic progression using transfer learning[EB/OL]. (2021-05-27)[2022-04-08]. https://www.preprints.org/manuscript/202105.0670/v1.
[28] López S, Smith-Zubiaga I, García de Galdeano A, et al. Comparison of the transcriptional profiles of melanocytes from dark and light skinned individuals under basal conditions and following ultraviolet-B irradiation[J]. PLoS One, 2015, 10(8): e0134911. DOI: 10.1371/journal.pone.0134911.