Identifying genes associated with Parkinson's disease plays an extremely important role in the diagnosis and treatment of Parkinson's disease. In recent years, based on the guilt-by-association hypothesis, many methods have been proposed to predict disease-related genes, but few of these methods are designed or used for Parkinson's disease gene prediction. In this paper, we propose a novel prediction method for Parkinson's disease gene prediction, named N2A-SVM. N2A-SVM includes three parts: extracting features of genes based on network, reducing the dimension using deep neural network, and predicting Parkinson's disease genes using a machine learning method. The evaluation test shows that N2A-SVM performs better than existing methods. Furthermore, we evaluate the significance of each step in the N2A-SVM algorithm and the influence of the hyper-parameters on the result. In addition, we train N2A-SVM on the recent dataset and used it to predict Parkinson's disease genes. The predicted top-rank genes can be verified based on literature study.

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Predicting Parkinson's Disease Genes Based on Node2vec and Autoencoder.

Since the establishment of the first biomedical ontology Gene Ontology (GO), the number of biomedical ontology has increased dramatically. Nowadays over 300 ontologies have been built including extensively used Disease Ontology (DO) and Human Phenotype Ontology (HPO). Because of the advantage of identifying novel relationships between terms, calculating similarity between ontology terms is one of the major tasks in this research area. Though similarities between terms within each ontology have been studied with in silico methods, term similarities across different ontologies were not investigated as deeply. The latest method took advantage of gene functional interaction network (GFIN) to explore such inter-ontology similarities of terms. However, it only used gene interactions and failed to make full use of the connectivity among gene nodes of the network. In addition, all existent methods are particularly designed for GO and their performances on the extended ontology community remain unknown. We proposed a method InfAcrOnt to infer similarities between terms across ontologies utilizing the entire GFIN. InfAcrOnt builds a term-gene-gene network which comprised ontology annotations and GFIN, and acquires similarities between terms across ontologies through modeling the information flow within the network by random walk. In our benchmark experiments on sub-ontologies of GO, InfAcrOnt achieves a high average area under the receiver operating characteristic curve (AUC) (0.9322 and 0.9309) and low standard deviations (1.8746e-6 and 3.0977e-6) in both human and yeast benchmark datasets exhibiting superior performance. Meanwhile, comparisons of InfAcrOnt results and prior knowledge on pair-wise DO-HPO terms and pair-wise DO-GO terms show high correlations. The experiment results show that InfAcrOnt significantly improves the performance of inferring similarities between terms across ontologies in benchmark set.

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InfAcrOnt: calculating cross-ontology term similarities using information flow by a random walk

The classification of cancer subtypes is of great importance to cancer disease diagnosis and therapy. Many supervised learning approaches have been applied to cancer subtype classification in the past few years, especially of deep learning based approaches. Recently, the deep forest model has been proposed as an alternative of deep neural networks to learn hyper-representations by using cascade ensemble decision trees. It has been proved that the deep forest model has competitive or even better performance than deep neural networks in some extent. However, the standard deep forest model may face overfitting and ensemble diversity challenges when dealing with small sample size and high-dimensional biology data. In this paper, we propose a deep learning model, so-called BCDForest, to address cancer subtype classification on small-scale biology datasets, which can be viewed as a modification of the standard deep forest model. The BCDForest distinguishes from the standard deep forest model with the following two main contributions: First, a named multi-class-grained scanning method is proposed to train multiple binary classifiers to encourage diversity of ensemble. Meanwhile, the fitting quality of each classifier is considered in representation learning. Second, we propose a boosting strategy to emphasize more important features in cascade forests, thus to propagate the benefits of discriminative features among cascade layers to improve the classification performance. Systematic comparison experiments on both microarray and RNA-Seq gene expression datasets demonstrate that our method consistently outperforms the state-of-the-art methods in application of cancer subtype classification. The multi-class-grained scanning and boosting strategy in our model provide an effective solution to ease the overfitting challenge and improve the robustness of deep forest model working on small-scale data. Our model provides a useful approach to the classification of cancer subtypes by using deep learning on high-dimensional and small-scale biology data.

/pdf/bcdforest-a-boosting-cascade-deep-forest-model-towards-the-1z73apzor1.pdf

BCDForest: a boosting cascade deep forest model towards the classification of cancer subtypes based on gene expression data

As a biomarker of inflammation, C-reactive protein (CRP) has attracted much attention due to its role in the incidence of type 2 diabetes mellitus (T2DM). Prospective studies have observed a positive correlation between the level of serum CRP and the incidence of T2DM. Recently, studies have reported that drugs for curing T2DM can also decrease the level of serum CRP. However, it is not yet clear whether high CRP levels cause T2DM. To evaluate this, we conducted a Mendelian randomization (MR) analysis using genetic variations as instrumental variables (IVs). Significantly associated single nucleotide polymorphisms (SNPs) of CRP were obtained from a genome-wide study and a replication study. Therein, 17,967 participants were utilized for the genome-wide association study (GWAS), and another 14,747 participants were utilized for the replication of identifying SNPs associated with CRP levels. The associations between SNPs and T2DM were from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. After removing SNPs in linkage disequilibrium (LD) and T2DM-related SNPs, the four remaining CRP-related SNPs were deemed as IVs. To evaluate the pooled influence of these IVs on the risk of developing T2DM through CRP, the penalized robust inverse-variance weighted (IVW) method was carried out. The combined result (OR 1.114048; 95% CI 1.058656 to 1.172338; P = 0.024) showed that high levels of CRP significantly increase the risk of T2DM. In the subsequent analysis of the relationship between CRP and type 1 diabetes mellitus (T1DM), the pooled result (OR 1.017145; 95% CI 0.9066489 to 1.14225; P = 0.909) supported that CRP levels cannot determine the risk of developing T1DM.

Exposing the Causal Effect of C-Reactive Protein on the Risk of Type 2 Diabetes Mellitus: A Mendelian Randomization Study.

In this paper, a computational method based on machine learning technique for identifying Alzheimer's disease genes is proposed. Compared with most existing machine learning based methods, existing methods predict Alzheimer's disease genes by using structural magnetic resonance imaging (MRI) technique. Most methods have attained acceptable results, but the cost is expensive and time consuming. Thus, we proposed a computational method for identifying Alzheimer disease genes by use of the sequence information of proteins, and classify the feature vectors by random forest. In the proposed method, the gene protein information is extracted by adaptive k-skip-n-gram features. The proposed method can attain the accuracy to 85.5% on the selected UniProt dataset, which has been demonstrated by the experimental results.

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k-Skip-n-Gram-RF: A Random Forest Based Method for Alzheimer's Disease Protein Identification.

It is critical yet remains to be challenging to make precise disease diagnosis from complex clinical features and highly heterogeneous genetic background. Recently, phenotype similarity has been effectively applied to model patient phenotype data. However, the existing measurements are revised based on the Gene Ontology-based term similarity models, which are not optimised for human phenotype ontologies. We propose a new similarity measure called PhenoSim. Our model includes a noise reduction component to model the noisy patient phenotype data, and a path-constrained Information Content-based method for phenotype semantics similarity measurement. Evaluation tests compared PhenoSim with four existing approaches. It showed that PhenoSim, could effectively improve the performance of HPO-based phenotype similarity measurement, thus increasing the accuracy of phenotype-based causative gene prediction and disease prediction.

A novel method to measure the semantic similarity of HPO terms

It is critical yet remains to be challenging to make right disease diagnosis based on complex clinical characteristic and heterogeneous genetic background. Recently, Human Phenotype Ontology (HPO)-based phenotype similarity has been widely used to aid disease diagnosis. However, the existing measurements are revised based on the Gene Ontology-based term similarity models, which are not optimized for human phenotype ontologies. We propose a new similarity measure called PhenoSim. Our model includes a noise reduction component to model the noisy patient phenotype data, and a path-constrained Information Content-based method for measuring phenotype semantics similarity. Evaluation tests showed that PhenoSim could improve the performance of HPO-based phenotype similarity measurement.

Yukai Shao

Papers

A novel method to measure the semantic similarity of HPO terms

Measuring phenotype semantic similarity using Human Phenotype Ontology