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Incorporating methylation genome information improves prediction accuracy for drug treatment responses.

ABSTRACT: BACKGROUND:An accumulation of evidence has revealed the important role of epigenetic factors in explaining the etiopathogenesis of human diseases. Several empirical studies have successfully incorporated methylation data into models for disease prediction. However, it is still a challenge to integrate different types of omics data into prediction models, and the contribution of methylation information to prediction remains to be fully clarified. RESULTS:A stratified drug-response prediction model was built based on an artificial neural network to predict the change in the circulating triglyceride level after fenofibrate intervention. Associated single-nucleotide polymorphisms (SNPs), methylation of selected cytosine-phosphate-guanine (CpG) sites, age, sex, and smoking status, were included as predictors. The model with selected SNPs achieved a mean 5-fold cross-validation prediction error rate of 43.65%. After adding methylation information into the model, the error rate dropped to 41.92%. The combination of significant SNPs, CpG sites, age, sex, and smoking status, achieved the lowest prediction error rate of 41.54%. CONCLUSIONS:Compared to using SNP data only, adding methylation data in prediction models slightly improved the error rate; further prediction error reduction is achieved by a combination of genome, methylation genome, and environmental factors.

SUBMITTER: Xia X

PROVIDER: S-EPMC6157255 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Incorporating methylation genome information improves prediction accuracy for drug treatment responses.

Xia Xiaoxuan X Weng Haoyi H Men Ruoting R Sun Rui R Zee Benny Chung Ying BCY Chong Ka Chun KC Wang Maggie Haitian MH

BMC genetics 20180917 Suppl 1

<h4>Background</h4>An accumulation of evidence has revealed the important role of epigenetic factors in explaining the etiopathogenesis of human diseases. Several empirical studies have successfully incorporated methylation data into models for disease prediction. However, it is still a challenge to integrate different types of omics data into prediction models, and the contribution of methylation information to prediction remains to be fully clarified.<h4>Results</h4>A stratified drug-response ...[more]

PMID: 30255773

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Project description:The accuracy of motion prediction, utilized to overcome the system latency of motion management radiotherapy systems, is hampered by irregularities present in the patients' respiratory pattern. Audiovisual (AV) biofeedback has been shown to reduce respiratory irregularities. The aim of this study was to test the hypothesis that AV biofeedback improves the accuracy of motion prediction.An AV biofeedback system combined with real-time respiratory data acquisition and MR images were implemented in this project. One-dimensional respiratory data from (1) the abdominal wall (30 Hz) and (2) the thoracic diaphragm (5 Hz) were obtained from 15 healthy human subjects across 30 studies. The subjects were required to breathe with and without the guidance of AV biofeedback during each study. The obtained respiratory signals were then implemented in a kernel density estimation prediction algorithm. For each of the 30 studies, five different prediction times ranging from 50 to 1400 ms were tested (150 predictions performed). Prediction error was quantified as the root mean square error (RMSE); the RMSE was calculated from the difference between the real and predicted respiratory data. The statistical significance of the prediction results was determined by the Student's t-test.Prediction accuracy was considerably improved by the implementation of AV biofeedback. Of the 150 respiratory predictions performed, prediction accuracy was improved 69% (103/150) of the time for abdominal wall data, and 78% (117/150) of the time for diaphragm data. The average reduction in RMSE due to AV biofeedback over unguided respiration was 26% (p < 0.001) and 29% (p < 0.001) for abdominal wall and diaphragm respiratory motion, respectively.This study was the first to demonstrate that the reduction of respiratory irregularities due to the implementation of AV biofeedback improves prediction accuracy. This would result in increased efficiency of motion management techniques affected by system latencies used in radiotherapy.

Project description:IntroductionMutations in BRCA1 and BRCA2 confer high risks of breast cancer and ovarian cancer. The risk prediction algorithm BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) may be used to compute the probabilities of carrying mutations in BRCA1 and BRCA2 and help to target mutation screening. Tumours from BRCA1 and BRCA2 mutation carriers display distinctive pathological features that could be used to better discriminate between BRCA1 mutation carriers, BRCA2 mutation carriers and noncarriers. In particular, oestrogen receptor (ER)-negative status, triple-negative (TN) status, and expression of basal markers are predictive of BRCA1 mutation carrier status.MethodsWe extended BOADICEA by treating breast cancer subtypes as distinct disease end points. Age-specific expression of phenotypic markers in a series of tumours from 182 BRCA1 mutation carriers, 62 BRCA2 mutation carriers and 109 controls from the Breast Cancer Linkage Consortium, and over 300,000 tumours from the general population obtained from the Surveillance Epidemiology, and End Results database, were used to calculate age-specific and genotype-specific incidences of each disease end point. The probability that an individual carries a BRCA1 or BRCA2 mutation given their family history and tumour marker status of family members was computed in sample pedigrees.ResultsThe cumulative risk of ER-negative breast cancer by age 70 for BRCA1 mutation carriers was estimated to be 55% and the risk of ER-positive disease was 18%. The corresponding risks for BRCA2 mutation carriers were 21% and 44% for ER-negative and ER-positive disease, respectively. The predicted BRCA1 carrier probabilities among ER-positive breast cancer cases were less than 1% at all ages. For women diagnosed with breast cancer below age 50 years, these probabilities rose to more than 5% in ER-negative breast cancer, 7% in TN disease and 24% in TN breast cancer expressing both CK5/6 and CK14 cytokeratins. Large differences in mutation probabilities were observed by combining ER status and other informative markers with family history.ConclusionsThis approach combines both full pedigree and tumour subtype data to predict BRCA1/2 carrier probabilities. Prediction of BRCA1/2 carrier status, and hence selection of women for mutation screening, may be substantially improved by combining tumour pathology with family history of cancer.

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Incorporating methylation genome information improves prediction accuracy for drug treatment responses.

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Incorporating methylation genome information improves prediction accuracy for drug treatment responses.

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