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Clusternomics: Integrative context-dependent clustering for heterogeneous datasets
- Source :
- PLoS Computational Biology, PLoS Computational Biology, Vol 13, Iss 10, p e1005781 (2017)
- Publication Year :
- 2016
-
Abstract
- Integrative clustering is used to identify groups of samples by jointly analysing multiple datasets describing the same set of biological samples, such as gene expression, copy number, methylation etc. Most existing algorithms for integrative clustering assume that there is a shared consistent set of clusters across all datasets, and most of the data samples follow this structure. However in practice, the structure across heterogeneous datasets can be more varied, with clusters being joined in some datasets and separated in others. In this paper, we present a probabilistic clustering method to identify groups across datasets that do not share the same cluster structure. The proposed algorithm, Clusternomics, identifies groups of samples that share their global behaviour across heterogeneous datasets. The algorithm models clusters on the level of individual datasets, while also extracting global structure that arises from the local cluster assignments. Clusters on both the local and the global level are modelled using a hierarchical Dirichlet mixture model to identify structure on both levels. We evaluated the model both on simulated and on real-world datasets. The simulated data exemplifies datasets with varying degrees of common structure. In such a setting Clusternomics outperforms existing algorithms for integrative and consensus clustering. In a real-world application, we used the algorithm for cancer subtyping, identifying subtypes of cancer from heterogeneous datasets. We applied the algorithm to TCGA breast cancer dataset, integrating gene expression, miRNA expression, DNA methylation and proteomics. The algorithm extracted clinically meaningful clusters with significantly different survival probabilities. We also evaluated the algorithm on lung and kidney cancer TCGA datasets with high dimensionality, again showing clinically significant results and scalability of the algorithm.<br />Author summary Integrative clustering is the task of identifying groups of samples by combining information from several datasets. An example of this task is cancer subtyping, where we cluster tumour samples based on several datasets, such as gene expression, proteomics and others. Most existing algorithms assume that all such datasets share a similar cluster structure, with samples outside these clusters treated as noise. The structure can, however, be much more heterogeneous: some meaningful clusters may appear only in some datasets. In the paper, we introduce the Clusternomics algorithm that identifies groups of samples across heterogeneous datasets. It models both cluster structure of individual datasets, and the global structure that appears as a combination of local structures. The algorithm uses probabilistic modelling to identify the groups and share information across the local and global levels. We evaluated the algorithm on both simulated and real world datasets, where the algorithm found clinically significant clusters with different survival outcomes.
- Subjects :
- 0301 basic medicine
Computer science
Gene Expression
computer.software_genre
01 natural sciences
Biochemistry
010104 statistics & probability
Breast Tumors
Medicine and Health Sciences
Cluster Analysis
Biology (General)
DNA methylation
Ecology
Applied Mathematics
Simulation and Modeling
Subtyping
Chromatin
Nucleic acids
Computational Theory and Mathematics
Oncology
Nephrology
Modeling and Simulation
Renal Cancer
Scalability
Physical Sciences
symbols
Epigenetics
Data mining
DNA modification
Algorithms
Chromatin modification
Research Article
Chromosome biology
Cell biology
QH301-705.5
Context (language use)
Breast Neoplasms
Research and Analysis Methods
Dirichlet distribution
Set (abstract data type)
03 medical and health sciences
Cellular and Molecular Neuroscience
symbols.namesake
Clustering Algorithms
Consensus clustering
Breast Cancer
Genetics
Humans
0101 mathematics
Cluster analysis
Non-coding RNA
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Gene Expression Profiling
Computational Biology
Biology and Life Sciences
Cancers and Neoplasms
DNA
Mixture model
Survival Analysis
Gene regulation
MicroRNAs
030104 developmental biology
ComputingMethodologies_PATTERNRECOGNITION
RNA
computer
Mathematics
Subjects
Details
- ISSN :
- 15537358
- Volume :
- 13
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS computational biology
- Accession number :
- edsair.doi.dedup.....a4a4f02c95d5ece03bd9ad72f20864e3