Pathway Activity Score Learning for Dimensionality Reduction of Gene Expression Data
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ABSTRACT:
SUBMITTER: Appice A
PROVIDER: S-EPMC7556388 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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Project description:Molecular gene-expression datasets consist of samples with tens of thousands of measured quantities (i.e., high dimensional data). However, lower-dimensional representations that retain the useful biological information do exist. We present a novel algorithm for such dimensionality reduction called Pathway Activity Score Learning (PASL). The major novelty of PASL is that the constructed features directly correspond to known molecular pathways (genesets in general) and can be interpreted as pathway activity scores. Hence, unlike PCA and similar methods, PASL's latent space has a fairly straightforward biological interpretation. PASL is shown to outperform in predictive performance the state-of-the-art method (PLIER) on two collections of breast cancer and leukemia gene expression datasets. PASL is also trained on a large corpus of 50000 gene expression samples to construct a universal dictionary of features across different tissues and pathologies. The dictionary validated on 35643 held-out samples for reconstruction error. It is then applied on 165 held-out datasets spanning a diverse range of diseases. The AutoML tool JADBio is employed to show that the predictive information in the PASL-created feature space is retained after the transformation. The code is available at https://github.com/mensxmachina/PASL.
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Project description:UnlabelledBackgroundMultifactor Dimensionality Reduction (MDR) has been widely applied to detect gene-gene (GxG) interactions associated with complex diseases. Existing MDR methods summarize disease risk by a dichotomous predisposing model (high-risk/low-risk) from one optimal GxG interaction, which does not take the accumulated effects from multiple GxG interactions into account.ResultsWe propose an Aggregated-Multifactor Dimensionality Reduction (A-MDR) method that exhaustively searches for and detects significant GxG interactions to generate an epistasis enriched gene network. An aggregated epistasis enriched risk score, which takes into account multiple GxG interactions simultaneously, replaces the dichotomous predisposing risk variable and provides higher resolution in the quantification of disease susceptibility. We evaluate this new A-MDR approach in a broad range of simulations. Also, we present the results of an application of the A-MDR method to a data set derived from Juvenile Idiopathic Arthritis patients treated with methotrexate (MTX) that revealed several GxG interactions in the folate pathway that were associated with treatment response. The epistasis enriched risk score that pooled information from 82 significant GxG interactions distinguished MTX responders from non-responders with 82% accuracy.ConclusionsThe proposed A-MDR is innovative in the MDR framework to investigate aggregated effects among GxG interactions. New measures (pOR, pRR and pChi) are proposed to detect multiple GxG interactions.
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Project description:Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.
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Project description:To detect false data injection attacks (FDIAs) in power grid reconstruction and solve the problem of high data dimension and bad abnormal data processing in the power system, thereby achieving safe and stable operation of the power grid system, this study introduces machine learning methods to explore the detection of FDIAs. First, through the utilization of the standard IEEE node system and the simulation of FDIAs under the condition of non-complete topology information, the construction of the attack data set is completed, and the MatPower tool is applied to simulate and analyze the data set. Second, based on the isolated Forest (iForest) abnormal score data processing algorithm combined with the Local Linear Embedding (LLE) data dimensionality reduction method, an algorithm for data feature extraction is constructed. Finally, based on the combination of the Convolutional Neural Network (CNN) and the Gated Recurrent Unit (GRU) network, an algorithm model for FDIAs detection is constructed. The results show that in the IEEE14-bus node and IEEE118-bus node systems, the overall distribution of the state estimated before and after the attack vector injection is consistent with the initial value. In the iFores algorithm, the number of iTree and the number of samples affect the extraction of abnormal score data. When the number of iTree n is determined to be 100, and the corresponding number of samples w is determined to be 10, the algorithm has the best detection effect. The FDIAs detection algorithm model based on CNN-GRU shows good detection effects under high attack intensity, with an accuracy rate of more than 95%, and its performance is better than other traditional detection algorithms. In this study, the bad data detection model based on deep learning has an active role in the realization of the safe and stable operation of the smart grid.
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Project description:Summarizing high-dimensional data using a small number of parameters is a ubiquitous first step in the analysis of neuronal population activity. Recently developed methods use "targeted" approaches that work by identifying multiple, distinct low-dimensional subspaces of activity that capture the population response to individual experimental task variables, such as the value of a presented stimulus or the behavior of the animal. These methods have gained attention because they decompose total neural activity into what are ostensibly different parts of a neuronal computation. However, existing targeted methods have been developed outside of the confines of probabilistic modeling, making some aspects of the procedures ad hoc, or limited in flexibility or interpretability. Here we propose a new model-based method for targeted dimensionality reduction based on a probabilistic generative model of the population response data. The low-dimensional structure of our model is expressed as a low-rank factorization of a linear regression model. We perform efficient inference using a combination of expectation maximization and direct maximization of the marginal likelihood. We also develop an efficient method for estimating the dimensionality of each subspace. We show that our approach outperforms alternative methods in both mean squared error of the parameter estimates, and in identifying the correct dimensionality of encoding using simulated data. We also show that our method provides more accurate inference of low-dimensional subspaces of activity than a competing algorithm, demixed PCA.
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