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. 2022 Mar 22;13:854752. doi: 10.3389/fgene.2022.854752

TABLE 3.

Low-level: Clustering-based unsupervised integration methods.

Approach Clustering method Macro category* Author Objective Omics data** Software***
Kernel-based Clustering Methods • L-MKKM (Localized Multiple Kernel K-Means) ModE Gönen and Margolin, (2014) Sample-subtyping CNV, DM, GE • Matlab code (https://github.com/mehmetgonen/lmkkmeans)
• SNF (Similarity Network Fusion) ModE Wang et al. (2014) Disease-subtyping Any Omics MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
CEPICS (https://rdrr.io/github/GaoLabXDU/CEPICS/)
CancerSubtypes (https://bioconductor.org/packages/release/bioc/html/CancerSubtypes.html)
• rMKL-LPP (regularized Multiple Kernels Learning with Locality Preserving Projections) ModE Speicher and Pfeifer, (2015) Disease-subtyping DM, MiE, GE • -
• WSNF (Weighted SNF) ModE Xu et al. (2016) Disease-subtyping MiE, GE CancerSubtypes (https://bioconductor.org/packages/release/bioc/html/CancerSubtypes.html)
• mixKernel ModE Mariette and Villa-Vialaneix, (2018) Sample-subtyping GE, MiE, DM mixKernel (https://cran.r-project.org/web/packages/mixKernel/index.html)
• DSSF (Deep Subspace Similarity Fusion) ModE Yang et al. (2018) Disease-subtyping DM, MiE, GE • -
• ANF (Affinity Network Fusion) ModE Ma and Zhang, (2018) Sample-subtyping DM, MiE, GE ANF (https://bioconductor.org/packages/release/bioc/html/ANF.html)
• NEMO (NEighborhood based Multi-Omics clustering) ModE Rappoport and Shamir, (2019) Disease-subtyping DM, MiE, GE NEMO (https://github.com/Shamir-Lab/NEMO)
MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
• ab-SNF (association-signal-annotation boosted SNF) ModE Ruan et al. (2019) Sample-subtyping DM, GE • R code (https://github.com/pfruan/abSNF/)
• MvNE (Multiview Neighborhood Embedding) ModE Mitra et al. (2020) Molecular-classification DM, MiE, GE • -
• INF (Integrative Network Fusion) DatE/ModE Chierici et al. (2020) Disease-subtyping, Disease-prediction CNV, MiE, GE, PE • Python/R code (https://gitlab.fbk.eu/MPBA/INF)
• SmSPK (Smoothed Shortest Path graph Kernel) ModE Tepeli et al. (2020) Sample-subtyping GE, PE, Mutation • Python code (https://github.com/tastanlab/pamogk)
• PAMOGK (PAthway-based MultiOmic Graph Kernel clustering) ModE Tepeli et al. (2020) Sample-subtyping GE, PE, Mutation • Python code (https://github.com/tastanlab/pamogk)
(Non-negative) Matrix Factorization-based Clustering Methods • iCluster ModE Shen et al. (2009) Disease-subtyping, Biomarker-identification CNV, GE iCluster (https://cran.r-project.org/web/packages/iCluster/index.html)
iClusterPlus (https://bioconductor.org/packages/release/bioc/html/iClusterPlus.html)
MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
CEPICS (https://rdrr.io/github/GaoLabXDU/CEPICS/)
CancerSubtypes (https://bioconductor.org/packages/release/bioc/html/CancerSubtypes.html)
• jNMF (Joint Non-negative Matrix Factorization) ModE Zhang et al. (2012) Disease-insight, Module-discovery MiE, DM, GE • -
• iClusterPlus ModE Mo et al. (2013) Disease-subtyping CNV, DM, GE iClusterPlus (https://bioconductor.org/packages/release/bioc/html/iClusterPlus.html)
Biomarker-identification
• FA (Factor Analysis) DatE Liu et al. (2013) Disease-subtyping MiE, GE, PE -
• moCluster ModE Meng et al. (2016) Disease-subtyping, Molecular-subtyping MiE, DM, PE mogsa (https://www.bioconductor.org/packages/release/bioc/html/mogsa.html)
MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
• JIVE (Joint and Individual Variation Explained) ModE O’Connell and Lock, (2016) Disease-subtyping MiE, DM, GE R.jive (https://cran.r-project.org/web/packages/r.jive/index.html)
• iNMF (integrative Non-negative Matrix Factorization) ModE Yang and Michailidis, (2016) Disease-subtyping MiE, DM, GE MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
• Python code (https://github.com/yangzi4/iNMF)
• PFA (Pattern Fusion Analysis) ModE Shi et al. (2017) Disease-subtyping MiE, DM, GE • -
• IS k -means (Integrative Sparse k-means) DatE Huo and Tseng, (2017) Disease-subtyping CNV, DM, GE • IS-Kmeans (https://github.com/Caleb-Huo/IS-Kmeans)
• MOGSA (Multi-Omics Gene-Set Analysis) DatE Meng et al. (2019) Disease-insight • GE, CNV, PE Mogsa (https://www.bioconductor.org/packages/release/bioc/html/mogsa.html)
• SCFA (Subtyping via Consensus Factor Analysis)  ModE Tran et al. (2020) Disease-subtyping • DM, MiE, GE • R code (https://github.com/duct317/SCFA)
Bayesian Clustering Methods • TMD (Transcriptional Modules Discovery) ModE Savage et al. (2010) Disease-subtyping GE, TF • -
• PARADIGM (PAthway Recognition Algorithm using Data Integration on Genomic Models) ModE Vaske et al. (2010) Disease-subtyping and Disease-insight CNV, GE, PE GIANT interface (http://giant.princeton.edu/)
• PSDF (Patient-Specific Data Fusion) ModE Yuan et al. (2011) Disease-subtyping CNV, GE • Matlab code (https://sites.google.com/site/patientspecificdatafusion/)
• MDI (Multiple Dataset Integration) ModE Kirk et al. (2012) Disease-subtyping GE, PE • Matlab code (https://warwick.ac.uk/fac/cross_fac/zeeman_institute/zeeman_research/software/)
• BCC (Bayesian Consensus Clustering) ModE Lock and Dunson, (2013) Disease-subtyping MiE, DM, GE, PE bayesCC (https://github.com/ttriche/bayesCC)
• LRAcluster (Low-Rank-Approximation) ModE Wu et al. (2015) Disease-subtyping CNV, DM, GE LRAcluster (http://lifeome.net/software/lracluster/)
MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
Multivariate and Other Clustering Methods • COCA (Cluster-Of-Cluster Assignment) ModE Hoadley et al. (2014) Disease-subtyping MiE, CNV, DM, GE, PE MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
coca (https://github.com/acabassi/coca)
• iPF (integrative Phenotyping Framework) DatE Kim et al. (2015) Sample-subtyping MiE, GE iPF (http://tsenglab.biostat.pitt.edu/software.htm)
• Clusternomics ModE Gabasova et al. (2017) Disease-subtyping MiE, DM, GE, PE Clusternomics (https://github.com/evelinag/clusternomics)
• PINS (Perturbation clustering for data INtegration and disease Subtyping) ModE Nguyen et al. (2017) Disease-subtyping MiE, CNV, DM, GE • -
• iDRW (integrative Directed Random Walk) DatE Kim et al. (2018) Disease-subtyping, Biomarker-discovery DM, GE • R code (https://github.com/sykim122/iDRW)
• PINSPlus ModE Nguyen et al. (2019) Disease-subtyping MiE, CNV, DM, GE PINSPlus (https://cran.r-project.org/web/packages/PINSPlus/index.html)
MOVICS (https://xlucpu.github.io/MOVICS/MOVICS-VIGNETTE.html)
• Subtype-GAN ModE Yang et al. (2021) Disease-subtyping MiE, CNV, DM, GE • R code (https://github.com/haiyang1986/Subtype-GAN)

*Macro categories include (A) Multi-step and Sequential Analysis (MS-SA), (B) Data-ensemble (DatE), (C) Model-ensemble (ModE). ** CNV: copy number variation, DM: DNA methylation, MiE: Micro RNA expression, GE: gene expression, TF: transcriptional factor, PE: Protein expression. ***R packages, unless otherwise stated.