Dataset Information

SPARCoC: a new framework for molecular pattern discovery and cancer gene identification.

ABSTRACT: It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust), which is based on a novel Common-background and Sparse-foreground Decomposition (CSD) model and the Maximum Block Improvement (MBI) co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust) and nonnegative matrix factorization (NMF). We apply SPARCoC to the study of lung adenocarcinoma (ADCA), an extremely heterogeneous histological type, and a significant challenge for molecular subtyping. For testing and verification, we use high quality gene expression profiling data of lung ADCA patients, and identify prognostic gene signatures which could cluster patients into subgroups that are significantly different in their overall survival (with p-values < 0.05). Our results are only based on gene expression profiling data analysis, without incorporating any other feature selection or clinical information; we are able to replicate our findings with completely independent datasets. SPARCoC is broadly applicable to large-scale genomic data to empower pattern discovery and cancer gene identification.

SUBMITTER: Ma S

PROVIDER: S-EPMC4359112 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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SPARCoC: a new framework for molecular pattern discovery and cancer gene identification.

Ma Shiqian S Johnson Daniel D Ashby Cody C Xiong Donghai D Cramer Carole L CL Moore Jason H JH Zhang Shuzhong S Huang Xiuzhen X

PloS one 20150313 3

It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust), which is based on a novel Common-background and Sparse-foreground Decomposition (CSD) model and the ...[more]

PMID: 25768286

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Project description:Algorithms for motif identification in sequence space have predominately been focused on recognizing patterns of a fixed length containing regions of perfect conservation with possible regions of unconstrained sequence. Such motifs can be found in everything from proteins with distinct active sites to non-coding RNAs with specific structural elements that are necessary to maintain functionality. In the event that an insertion/deletion has occurred within an unconstrained portion of the pattern, it is possible that the pattern retains its functionality. In such a case the length of the pattern is now variable and may be overlooked when utilizing existing motif detection methods. The Pattern Island Detection Algorithm (PIDA) presented here has been developed to recognize patterns that have occurrences of varying length within sequences of any size alphabet. PIDA works by identifying all regions of perfect conservation (for lengths longer than a user-specified threshold), and then builds those conservation "islands" into fixed-length patterns. Next the algorithm modifies these fixed-length patterns by identifying additional (and different) islands that can be incorporated into each pattern through insertions/deletions within the "water" separating the islands. To provide some benchmarks for this analysis, PIDA was used to search for patterns within randomly generated sequences as well as sequences known to contain conserved patterns. For each of the patterns found, the statistical significance is calculated based upon the pattern's likelihood to appear by chance, thus providing a means to determine those patterns which are likely to have a functional role. The PIDA approach to motif finding is designed to perform best when searching for patterns of variable length although it is also able to identify patterns of a fixed length. PIDA has been created to be as generally applicable as possible since there are a variety of sequence problems of this type. The algorithm was implemented in C++ and is freely available upon request from the authors.

Dataset Information

SPARCoC: a new framework for molecular pattern discovery and cancer gene identification.

Publications

SPARCoC: a new framework for molecular pattern discovery and cancer gene identification.

Similar Datasets

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