Dataset Information

Multi-OMICs and Genome Editing Perspectives on Liver Cancer Signaling Networks.

ABSTRACT: The advent of the human genome sequence and the resulting ~20,000 genes provide a crucial framework for a transition from traditional biology to an integrative "OMICs" arena (Lander et al., 2001; Venter et al., 2001; Kitano, 2002). This brings in a revolution for cancer research, which now enters a big data era. In the past decade, with the facilitation by next-generation sequencing, there have been a huge number of large-scale sequencing efforts, such as The Cancer Genome Atlas (TCGA), the HapMap, and the 1000 genomes project. As a result, a deluge of genomic information becomes available from patients stricken by a variety of cancer types. The list of cancer-associated genes is ever expanding. New discoveries are made on how frequent and highly penetrant mutations, such as those in the telomerase reverse transcriptase (TERT) and TP53, function in cancer initiation, progression, and metastasis. Most genes with relatively frequent but weakly penetrant cancer mutations still remain to be characterized. In addition, genes that harbor rare but highly penetrant cancer-associated mutations continue to emerge. Here, we review recent advances related to cancer genomics, proteomics, and systems biology and suggest new perspectives in targeted therapy and precision medicine.

SUBMITTER: Lin S

PROVIDER: S-EPMC4923561 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-OMICs and Genome Editing Perspectives on Liver Cancer Signaling Networks.

Lin Shengda S Yin Yi A YA Jiang Xiaoqian X Sahni Nidhi N Yi Song S

BioMed research international 20160614

The advent of the human genome sequence and the resulting ~20,000 genes provide a crucial framework for a transition from traditional biology to an integrative "OMICs" arena (Lander et al., 2001; Venter et al., 2001; Kitano, 2002). This brings in a revolution for cancer research, which now enters a big data era. In the past decade, with the facilitation by next-generation sequencing, there have been a huge number of large-scale sequencing efforts, such as The Cancer Genome Atlas (TCGA), the HapM ...[more]

PMID: 27403431

Similar Datasets

Project description:BackgroundCancer is a complex and heterogeneous disease with many possible genetic and environmental causes. The same treatment for patients of the same cancer type often results in different outcomes in terms of efficacy and side effects of the treatment. Thus, the molecular characterization of individual cancer patients is increasingly important to find an effective treatment. Recently a few methods have been developed to construct cancer sample-specific gene networks based on the difference in the mRNA expression levels between the cancer sample and reference samples.MethodsWe constructed a patient-specific network with multi-omics data based on the difference between a reference network and a perturbed reference network by the patient. A network specific to a group of patients was obtained using the average change in correlation coefficients and node degree of patient-specific networks of the group.ResultsIn this paper, we present a new method for constructing cancer patient-specific and group-specific gene networks with multi-omics data. The main differences of our method from previous ones are as follows: (1) networks are constructed with multi-omics (mRNA expression, copy number variation, DNA methylation and microRNA expression) data rather than with mRNA expression data alone, (2) background networks are constructed with both normal samples and cancer samples of the specified type to extract cancer-specific gene correlations, and (3) both patient individual-specific networks and patient group-specific networks can be constructed. The results of evaluating our method with several types of cancer show that it constructs more informative and accurate gene networks than previous methods.ConclusionsThe results of evaluating our method with extensive data of seven cancer types show that the difference of gene correlations between the reference samples and a patient sample is a more predictive feature than mRNA expression levels and that gene networks constructed with multi-omics data show a better performance than those with single omics data in predicting cancer for most cancer types. Our approach will be useful for finding genes and gene pairs to tailor treatments to individual characteristics.

Project description:Accurate cancer subtype prediction is crucial for personalized medicine. Integrating multi-omics data represents a viable approach to comprehending the intricate pathophysiology of complex diseases like cancer. Conventional machine learning techniques are not ideal for analyzing the complex interrelationships among different categories of omics data. Numerous models have been suggested using graph-based learning to uncover veiled representations and network formations unique to distinct types of omics data to heighten predictions regarding cancers and characterize patients' profiles, amongst other applications aimed at improving disease management in medical research. The existing graph-based state-of-the-art multi-omics integration approaches for cancer subtype prediction, MOGONET, and SUPREME, use a graph convolutional network (GCN), which fails to consider the level of importance of neighboring nodes on a particular node. To address this gap, we hypothesize that paying attention to each neighbor or providing appropriate weights to neighbors based on their importance might improve the cancer subtype prediction. The natural choice to determine the importance of each neighbor of a node in a graph is to explore the graph attention network (GAT). Here, we propose MOGAT, a novel multi-omics integration approach, leveraging GAT models that incorporate graph-based learning with an attention mechanism. MOGAT utilizes a multi-head attention mechanism to extract appropriate information for a specific sample by assigning unique attention coefficients to neighboring samples. Based on our knowledge, our group is the first to explore GAT in multi-omics integration for cancer subtype prediction. To evaluate the performance of MOGAT in predicting cancer subtypes, we explored two sets of breast cancer data from TCGA and METABRIC. Our proposed approach, MOGAT, outperforms MOGONET by 32% to 46% and SUPREME by 2% to 16% in cancer subtype prediction in different scenarios, supporting our hypothesis. Our results also showed that GAT embeddings provide a better prognosis in differentiating the high-risk group from the low-risk group than raw features.

Dataset Information

Multi-OMICs and Genome Editing Perspectives on Liver Cancer Signaling Networks.

Publications

Multi-OMICs and Genome Editing Perspectives on Liver Cancer Signaling Networks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets