Graph Embedding Methods for Multiple-Omics Data Analysis

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Bootstrapped R2 scores for genes involved in the renin-angiotensin system for lung, heart (left ventricle), kidney (cortex), and pancreas. The input variables are the expressions of genes in whole blood belonging to the chemokine, TNF, and TGF-β pathways.
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Visualization of one-hot encoded functional features and the learned embeddings. (A) One-hot encode representation of functional data KEGG/GO terms; (B) the learned network embeddings from a protein-protein network; (C) the learned embeddings of functional data using word2vec; (D) the combined network and functional embeddings.
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Breast cancer is the most common malignancy in women, and because it has a high mortality rate, it is urgent to develop computational methods to increase the accuracy of breast cancer survival predictive models. Although multi-omics data such as gene expression have been extensively used in recent studies, the accurate prognosis of breast cancer remains a challenge. Somatic mutations are another important and promising data source for studying cancer development, and its effect on the prognosis of breast cancer remains to be further explored. Meanwhile, these omics datasets are high-dimensional and redundant. Therefore, we adopted multiple kernel learning (MKL) to efficiently integrate somatic mutation to currently molecular data including gene expression, copy number variation (CNV), methylation, and protein expression data for the prediction of breast cancer survival. Before integration, the maximum relevance minimum redundancy (mRMR) feature selection method was utilized to select features that present high relevance to survival and low redundancy among themselves for each type of data. The experimental results demonstrated that the proposed method achieved the most optimal performance and there was a remarkable improvement in the prediction performance when somatic mutations were included, indicating that somatic mutations are critical for improving breast cancer survival predictions. Moreover, mRMR was superior to other feature selection methods used in previous studies. Furthermore, MKL outperformed the other traditional classifiers in multi-omics data integration. Our analysis indicated that through employing promising omics data such as somatic mutations and harnessing the power of proper feature selection methods and effective integration frameworks, the breast cancer survival predictive accuracy can be further increased, thereby providing a more optimal clinical diagnosis and more effective treatment for breast cancer patients.

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23 citations
Original Research
15 January 2021
Identification of Common Genes and Pathways in Eight Fibrosis Diseases
Chang Gu
6 more and 
Tao Huang
The number of overlapped genes among the eight fibrotic diseases. A circular plot illustrating all possible intersections and the corresponding statistics. The eight circles from inside to outside represent the eight fibrotic diseases (1, eye fibrosis; 2, heart fibrosis; 3, hepatic fibrosis; 4, intestinal fibrosis; 5, lung fibrosis; 6, pancreas fibrosis; 7, renal fibrosis; and 8, skin fibrosis), respectively. The height of the bars in the outer layer is proportional to the intersection sizes, as indicated by the numbers on the top of the bars. The color intensity of the bars represents the P-value significance of the intersections.

Acute and chronic inflammation often leads to fibrosis, which is also the common and final pathological outcome of chronic inflammatory diseases. To explore the common genes and pathogenic pathways among different fibrotic diseases, we collected all the reported genes of the eight fibrotic diseases: eye fibrosis, heart fibrosis, hepatic fibrosis, intestinal fibrosis, lung fibrosis, pancreas fibrosis, renal fibrosis, and skin fibrosis. We calculated the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment scores of all fibrotic disease genes. Each gene was encoded using KEGG and GO enrichment scores, which reflected how much a gene can affect this function. For each fibrotic disease, by comparing the KEGG and GO enrichment scores between reported disease genes and other genes using the Monte Carlo feature selection (MCFS) method, the key KEGG and GO features were identified. We compared the gene overlaps among eight fibrotic diseases and connective tissue growth factor (CTGF) was finally identified as the common key molecule. The key KEGG and GO features of the eight fibrotic diseases were all screened by MCFS method. Moreover, we interestingly found overlaps of pathways between renal fibrosis and skin fibrosis, such as GO:1901890-positive regulation of cell junction assembly, as well as common regulatory genes, such as CTGF, which is the key molecule regulating fibrogenesis. We hope to offer a new insight into the cellular and molecular mechanisms underlying fibrosis and therefore help leading to the development of new drugs, which specifically delay or even improve the symptoms of fibrosis.

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