Approach: 3. Integrative Analysis

The construction of cellular morphometric context at patient level in a large cohort enables the integrative analysis with both clinical and molecular information, which contains the components as follows,

  • Identification of cellular morphometric subtypes/clusters: consensus clustering \cite{Monti03} is performed for identifying subtypes/clusters across patients. The input of consensus clustering are the \textcolor{black}{cellular morphometric context} at the patient level. Consensus clustering aggregates consensus across multiple runs for a base clustering algorithm. Moreover, it provides a visualization tool to explore the number of clusters in the data, as well as assessing the stability of the discovered clusters.
  • Survival analysis: Cox proportional hazards (PH) regression model is used for survival analysis.
  • Enrichment analysis: Fisher's exact test is used for the enrichment analysis between cellular morphometric context subtypes and genomic subtypes.
  • Genomic association: linear models are used for assessing differential expression of genes between subtypes of cellular morphometric context, and the correlation between genes and cellular morphometric types.