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Towards integrated oncogenic marker recognition through mutual information-based statistically significant feature extraction: an association rule mining based study on cancer expression and methylation profiles.

ABSTRACT: Background:Marker detection is an important task in complex disease studies. Here we provide an association rule mining (ARM) based approach for identifying integrated markers through mutual information (MI) based statistically significant feature extraction, and apply it to acute myeloid leukemia (AML) and prostate carcinoma (PC) gene expression and methylation profiles. Methods:We first collect the genes having both expression and methylation values in AML as well as PC. Next, we run Jarque-Bera normality test on the expression/methylation data to divide the whole dataset into two parts: one that ollows normal distribution and the other that does not follow normal distribution. Thus, we have now four parts of the dataset: normally distributed expression data, normally distributed methylation data, non-normally distributed expression data, and non-normally distributed methylated data. A feature-extraction technique, "mRMR" is then utilized on each part. This results in a list of top-ranked genes. Next, we apply Welch t-test (parametric test) and Shrink t-test (non-parametric test) on the expression/methylation data for the top selected normally distributed genes and non-normally distributed genes, respectively. We then use a recent weighted ARM method, "RANWAR" to combine all/specific resultant genes to generate top oncogenic rules along with respective integrated markers. Finally, we perform literature search as well as KEGG pathway and Gene-Ontology (GO) analyses using Enrichr database for in silico validation of the prioritized oncogenes as the markers and labeling the markers as existing or novel. Results:The novel markers of AML are {ABCB11??KRT17?} (i.e., ABCB11 as up-regulated, & KRT17 as down-regulated), and {AP1S1-?KRT17??NEIL2-?DYDC1?}) (i.e., AP1S1 and NEIL2 both as hypo-methylated, & KRT17 and DYDC1 both as down-regulated). The novel marker of PC is {UBIAD1¶?APBA2‡?C4orf31‡} (i.e., UBIAD1 as up-regulated and hypo-methylated, & APBA2 and C4orf31 both as down-regulated and hyper-methylated). Conclusion:The identified novel markers might have critical roles in AML as well as PC. The approach can be applied to other complex disease.

SUBMITTER: Mallik S

PROVIDER: S-EPMC6135253 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Towards integrated oncogenic marker recognition through mutual information-based statistically significant feature extraction: an association rule mining based study on cancer expression and methylation profiles.

Mallik Saurav S Zhao Zhongming Z

Quantitative biology (Beijing, China) 20171123 4

<h4>Background</h4>Marker detection is an important task in complex disease studies. Here we provide an association rule mining (ARM) based approach for identifying integrated markers through mutual information (MI) based statistically significant feature extraction, and apply it to acute myeloid leukemia (AML) and prostate carcinoma (PC) gene expression and methylation profiles.<h4>Methods</h4>We first collect the genes having both expression and methylation values in AML as well as PC. Next, w ...[more]

PMID: 30221015

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Project description:MotivationMost modern intensive care units record the physiological and vital signs of patients. These data can be used to extract signatures, commonly known as biomarkers, that help physicians understand the biological complexity of many syndromes. However, most biological biomarkers suffer from either poor predictive performance or weak explanatory power. Recent developments in time series classification focus on discovering shapelets, i.e. subsequences that are most predictive in terms of class membership. Shapelets have the advantage of combining a high predictive performance with an interpretable component-their shape. Currently, most shapelet discovery methods do not rely on statistical tests to verify the significance of individual shapelets. Therefore, identifying associations between the shapelets of physiological biomarkers and patients that exhibit certain phenotypes of interest enables the discovery and subsequent ranking of physiological signatures that are interpretable, statistically validated and accurate predictors of clinical endpoints.ResultsWe present a novel and scalable method for scanning time series and identifying discriminative patterns that are statistically significant. The significance of a shapelet is evaluated while considering the problem of multiple hypothesis testing and mitigating it by efficiently pruning untestable shapelet candidates with Tarone's method. We demonstrate the utility of our method by discovering patterns in three of a patient's vital signs: heart rate, respiratory rate and systolic blood pressure that are indicators of the severity of a future sepsis event, i.e. an inflammatory response to an infective agent that can lead to organ failure and death, if not treated in time.Availability and implementationWe make our method and the scripts that are required to reproduce the experiments publicly available at https://github.com/BorgwardtLab/S3M.Supplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Towards integrated oncogenic marker recognition through mutual information-based statistically significant feature extraction: an association rule mining based study on cancer expression and methylation profiles.

Publications

Towards integrated oncogenic marker recognition through mutual information-based statistically significant feature extraction: an association rule mining based study on cancer expression and methylation profiles.

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