Dataset Information

Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study.

ABSTRACT: BACKGROUND: Gene silencing using exogenous small interfering RNAs (siRNAs) is now a widespread molecular tool for gene functional study and new-drug target identification. The key mechanism in this technique is to design efficient siRNAs that incorporated into the RNA-induced silencing complexes (RISC) to bind and interact with the mRNA targets to repress their translations to proteins. Although considerable progress has been made in the computational analysis of siRNA binding efficacy, few joint analysis of different RNAi experiments conducted under different experimental scenarios has been done in research so far, while the joint analysis is an important issue in cross-platform siRNA efficacy prediction. A collective analysis of RNAi mechanisms for different datasets and experimental conditions can often provide new clues on the design of potent siRNAs. RESULTS: An elegant multi-task learning paradigm for cross-platform siRNA efficacy prediction is proposed. Experimental studies were performed on a large dataset of siRNA sequences which encompass several RNAi experiments recently conducted by different research groups. By using our multi-task learning method, the synergy among different experiments is exploited and an efficient multi-task predictor for siRNA efficacy prediction is obtained. The 19 most popular biological features for siRNA according to their jointly importance in multi-task learning were ranked. Furthermore, the hypothesis is validated out that the siRNA binding efficacy on different messenger RNAs(mRNAs) have different conditional distribution, thus the multi-task learning can be conducted by viewing tasks at an "mRNA"-level rather than at the "experiment"-level. Such distribution diversity derived from siRNAs bound to different mRNAs help indicate that the properties of target mRNA have important implications on the siRNA binding efficacy. CONCLUSIONS: The knowledge gained from our study provides useful insights on how to analyze various cross-platform RNAi data for uncovering of their complex mechanism.

SUBMITTER: Liu Q

PROVIDER: S-EPMC2873531 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study.

Liu Qi Q Xu Qian Q Zheng Vincent W VW Xue Hong H Cao Zhiwei Z Yang Qiang Q

BMC bioinformatics 20100410

<h4>Background</h4>Gene silencing using exogenous small interfering RNAs (siRNAs) is now a widespread molecular tool for gene functional study and new-drug target identification. The key mechanism in this technique is to design efficient siRNAs that incorporated into the RNA-induced silencing complexes (RISC) to bind and interact with the mRNA targets to repress their translations to proteins. Although considerable progress has been made in the computational analysis of siRNA binding efficacy, f ...[more]

PMID: 20380733

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Project description:Many machine learning and pattern classification methods have been applied to the diagnosis of Alzheimer's disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). Recently, rather than predicting categorical variables as in classification, several pattern regression methods have also been used to estimate continuous clinical variables from brain images. However, most existing regression methods focus on estimating multiple clinical variables separately and thus cannot utilize the intrinsic useful correlation information among different clinical variables. On the other hand, in those regression methods, only a single modality of data (usually only the structural MRI) is often used, without considering the complementary information that can be provided by different modalities. In this paper, we propose a general methodology, namely multi-modal multi-task (M3T) learning, to jointly predict multiple variables from multi-modal data. Here, the variables include not only the clinical variables used for regression but also the categorical variable used for classification, with different tasks corresponding to prediction of different variables. Specifically, our method contains two key components, i.e., (1) a multi-task feature selection which selects the common subset of relevant features for multiple variables from each modality, and (2) a multi-modal support vector machine which fuses the above-selected features from all modalities to predict multiple (regression and classification) variables. To validate our method, we perform two sets of experiments on ADNI baseline MRI, FDG-PET, and cerebrospinal fluid (CSF) data from 45 AD patients, 91 MCI patients, and 50 healthy controls (HC). In the first set of experiments, we estimate two clinical variables such as Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), as well as one categorical variable (with value of 'AD', 'MCI' or 'HC'), from the baseline MRI, FDG-PET, and CSF data. In the second set of experiments, we predict the 2-year changes of MMSE and ADAS-Cog scores and also the conversion of MCI to AD from the baseline MRI, FDG-PET, and CSF data. The results on both sets of experiments demonstrate that our proposed M3T learning scheme can achieve better performance on both regression and classification tasks than the conventional learning methods.

Dataset Information

Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study.

Publications

Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study.

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