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Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials.

ABSTRACT: Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell-material interactions and suggest alternative research routes for evaluating biomaterials to improve their design.

SUBMITTER: Autefage H

PROVIDER: S-EPMC4394289 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials.

Autefage Hélène H Gentleman Eileen E Littmann Elena E Hedegaard Martin A B MA Von Erlach Thomas T O'Donnell Matthew M Burden Frank R FR Winkler David A DA Stevens Molly M MM

Proceedings of the National Academy of Sciences of the United States of America 20150323 14

Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by ...[more]

PMID: 25831522

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Project description:In this work, we propose a novel Feature Selection framework called Sparse-Modeling Based Approach for Class Specific Feature Selection (SMBA-CSFS), that simultaneously exploits the idea of Sparse Modeling and Class-Specific Feature Selection. Feature selection plays a key role in several fields (e.g., computational biology), making it possible to treat models with fewer variables which, in turn, are easier to explain, by providing valuable insights on the importance of their role, and likely speeding up the experimental validation. Unfortunately, also corroborated by the no free lunch theorems, none of the approaches in literature is the most apt to detect the optimal feature subset for building a final model, thus it still represents a challenge. The proposed feature selection procedure conceives a two-step approach: (a) a sparse modeling-based learning technique is first used to find the best subset of features, for each class of a training set; (b) the discovered feature subsets are then fed to a class-specific feature selection scheme, in order to assess the effectiveness of the selected features in classification tasks. To this end, an ensemble of classifiers is built, where each classifier is trained on its own feature subset discovered in the previous phase, and a proper decision rule is adopted to compute the ensemble responses. In order to evaluate the performance of the proposed method, extensive experiments have been performed on publicly available datasets, in particular belonging to the computational biology field where feature selection is indispensable: the acute lymphoblastic leukemia and acute myeloid leukemia, the human carcinomas, the human lung carcinomas, the diffuse large B-cell lymphoma, and the malignant glioma. SMBA-CSFS is able to identify/retrieve the most representative features that maximize the classification accuracy. With top 20 and 80 features, SMBA-CSFS exhibits a promising performance when compared to its competitors from literature, on all considered datasets, especially those with a higher number of features. Experiments show that the proposed approach may outperform the state-of-the-art methods when the number of features is high. For this reason, the introduced approach proposes itself for selection and classification of data with a large number of features and classes.

Project description:Background:Machine learning methods have gained popularity and practicality in identifying linear and non-linear effects of variants associated with complex disease/traits. Detection of epistatic interactions still remains a challenge due to the large number of features and relatively small sample size as input, thus leading to the so-called "short fat data" problem. The efficiency of machine learning methods can be increased by limiting the number of input features. Thus, it is very important to perform variable selection before searching for epistasis. Many methods have been evaluated and proposed to perform feature selection, but no single method works best in all scenarios. We demonstrate this by conducting two separate simulation analyses to evaluate the proposed collective feature selection approach. Results:Through our simulation study we propose a collective feature selection approach to select features that are in the "union" of the best performing methods. We explored various parametric, non-parametric, and data mining approaches to perform feature selection. We choose our top performing methods to select the union of the resulting variables based on a user-defined percentage of variants selected from each method to take to downstream analysis. Our simulation analysis shows that non-parametric data mining approaches, such as MDR, may work best under one simulation criteria for the high effect size (penetrance) datasets, while non-parametric methods designed for feature selection, such as Ranger and Gradient boosting, work best under other simulation criteria. Thus, using a collective approach proves to be more beneficial for selecting variables with epistatic effects also in low effect size datasets and different genetic architectures. Following this, we applied our proposed collective feature selection approach to select the top 1% of variables to identify potential interacting variables associated with Body Mass Index (BMI) in ~?44,000 samples obtained from Geisinger's MyCode Community Health Initiative (on behalf of DiscovEHR collaboration). Conclusions:In this study, we were able to show that selecting variables using a collective feature selection approach could help in selecting true positive epistatic variables more frequently than applying any single method for feature selection via simulation studies. We were able to demonstrate the effectiveness of collective feature selection along with a comparison of many methods in our simulation analysis. We also applied our method to identify non-linear networks associated with obesity.

Project description:BACKGROUND:Feature selection in class-imbalance learning has gained increasing attention in recent years due to the massive growth of high-dimensional class-imbalanced data across many scientific fields. In addition to reducing model complexity and discovering key biomarkers, feature selection is also an effective method of combating overlapping which may arise in such data and become a crucial aspect for determining classification performance. However, ordinary feature selection techniques for classification can not be simply used for addressing class-imbalanced data without any adjustment. Thus, more efficient feature selection technique must be developed for complicated class-imbalanced data, especially in the context of high-dimensionality. RESULTS:We proposed an algorithm called sssHD to achieve stable sparse feature selection applied it to complicated class-imbalanced data. sssHD is based on the Hellinger distance (HD) coupled with sparse regularization techniques. We stated that Hellinger distance is not only class-insensitive but also translation-invariant. Simulation result indicates that HD-based selection algorithm is effective in recognizing key features and control false discoveries for class-imbalance learning. Five gene expression datasets are also employed to test the performance of the sssHD algorithm, and a comparison with several existing selection procedures is performed. The result shows that sssHD is highly competitive in terms of five assessment metrics. In addition, sssHD presents limited differences between performing and not performing re-balance preprocessing. CONCLUSIONS:sssHD is a practical feature selection method for high-dimensional class-imbalanced data, which is simple and can be an alternative for performing feature selection in class-imbalanced data. sssHD can be easily extended by connecting it with different re-balance preprocessing, different sparse regularization structures as well as different classifiers. As such, the algorithm is extremely general and has a wide range of applicability.

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Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials.

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Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials.

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