iCluster

Overview

iCluster is a probabilistic latent variable model for joint dimensionality reduction and clustering of multi-platform genomic data. It simultaneously integrates copy-number, mutation, methylation, and expression data across the same sample set to define integrative subtypes that reflect concordant signals across data types.

Used by

  • Applied to 333 cutaneous melanoma samples integrating SNP6 copy-number, WES mutations, Illumina 450K methylation, miRNA-seq, and RNA-seq data; identified three integrative clusters including an Immune-mRNA + low-CN + normal-like methylation cluster, a hypomethylation + MITF-expression cluster, and a CIMP + keratin + miRNA-cluster-3 group. PMID:26091043
  • Integrative clustering used to define seven mutually exclusive molecular subtypes (ERG/ETV1/ETV4/FLI1 fusions, SPOP/FOXA1/IDH1 mutations) across 333 primary prostate adenocarcinomas in the TCGA molecular taxonomy study PMID:26544944.
  • iCluster integrative clustering applied across SCNA, methylation, mRNA, and miRNA platforms in the TCGA esophageal/stomach study; cleanly separated squamous from adenocarcinoma histologies and defined three ESCC molecular subtypes (ESCC1, ESCC2, ESCC3) PMID:28052061.
  • iClusterPlus integrative clustering applied to 94 CCA samples with all four data types (sSNVs/indels, sCNAs, mRNA, methylation), validated by randomized subsampling and expanded to 121 samples with 90% cluster-prediction accuracy PMID:28667006
  • iCluster used for cross-platform integrative clustering (WES, RNA-seq, methylation, RPPA, SNP6) of 206 TCGA sarcomas; separated LMS into ULMS vs STLMS clusters and defined STLMS C1 (worse RFS, p=0.0002) vs C2 molecular subtypes PMID:29100075

Notes

  • Produces integrative cluster assignments that can differ from single-platform subtypes (e.g., transcriptomic clusters).
  • Core set of 199 samples with complete six-platform data used for iCluster analysis in TCGA SKCM.

Sources

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