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Cancer heterogeneity analysis is essential for precision medicine. Most of the existing heterogeneity analyses only consider a single type of data and ignore the possible sparsity of important features. In cancer clinical practice, it has been suggested that two types of data, pathological imaging and omics data, are commonly collected and can produce hierarchical heterogeneous structures, in which the refined sub‐subgroup structure determined by omics features can be nested in the rough subgroup structure determined by the imaging features. Moreover, sparsity pursuit has extraordinary significance and is more challenging for heterogeneity analysis, because the important features may not be the same in different subgroups, which is ignored by the existing heterogeneity analyses. Fortunately, rich information from previous literature (for example, those deposited in PubMed) can be used to assist feature selection in the present study. Advancing from the existing analyses, in this study, we propose a novel sparse hierarchical heterogeneity analysis framework, which can integrate two types of features and incorporate prior knowledge to improve feature selection. The proposed approach has satisfactory statistical properties and competitive numerical performance. A TCGA real data analysis demonstrates the practical value of our approach in analyzing data heterogeneity and sparsity.
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Biomarker‐guided heterogeneity analysis of genetic regulations via multivariate sparse fusion
Heterogeneity is a hallmark of many complex diseases. There are multiple ways of defining heterogeneity, among which the heterogeneity in genetic regulations, for example, gene expressions (GEs) by copy number variations (CNVs), and methylation, has been suggested but little investigated. Heterogeneity in genetic regulations can be linked with disease severity, progression, and other traits and is biologically important. However, the analysis can be very challenging with the high dimensionality of both sides of regulation as well as sparse and weak signals. In this article, we consider the scenario where subjects form unknown subgroups, and each subgroup has unique genetic regulation relationships. Further, such heterogeneity is “guided” by a known biomarker. We develop a multivariate sparse fusion (MSF) approach, which innovatively applies the penalized fusion technique to simultaneously determine the number and structure of subgroups and regulation relationships within each subgroup. An effective computational algorithm is developed, and extensive simulations are conducted. The analysis of heterogeneity in the GE‐CNV regulations in melanoma and GE‐methylation regulations in stomach cancer using the TCGA data leads to interesting findings.
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- Award ID(s):
- 1916251
- PAR ID:
- 10449661
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Statistics in Medicine
- Volume:
- 40
- Issue:
- 17
- ISSN:
- 0277-6715
- Format(s):
- Medium: X Size: p. 3915-3936
- Size(s):
- p. 3915-3936
- Sponsoring Org:
- National Science Foundation
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