EXTRACTING GENE EXPRESSION PROFILES COMMON TO COLON AND PANCREATIC ADENOCARCINOMA USING SIMULTANEOUS NONNEGATIVE MATRIX FACTORIZATION

Author(s):  
LIVIU BADEA
2019 ◽  
Author(s):  
Daiwei Tang ◽  
Seyoung Park ◽  
Hongyu Zhao

Abstract Motivation A number of computational methods have been proposed recently to profile tumor microenvironment (TME) from bulk RNA data, and they have proved useful for understanding microenvironment differences among therapeutic response groups. However, these methods are not able to account for tumor proportion nor variable mRNA levels across cell types. Results In this article, we propose a Nonnegative Matrix Factorization-based Immune-TUmor MIcroenvironment Deconvolution (NITUMID) framework for TME profiling that addresses these limitations. It is designed to provide robust estimates of tumor and immune cells proportions simultaneously, while accommodating mRNA level differences across cell types. Through comprehensive simulations and real data analyses, we demonstrate that NITUMID not only can accurately estimate tumor fractions and cell types’ mRNA levels, which are currently unavailable in other methods; it also outperforms most existing deconvolution methods in regular cell type profiling accuracy. Moreover, we show that NITUMID can more effectively detect clinical and prognostic signals from gene expression profiles in tumor than other methods. Availability and implementation The algorithm is implemented in R. The source code can be downloaded at https://github.com/tdw1221/NITUMID. Supplementary information Supplementary data are available at Bioinformatics online.


2014 ◽  
Vol 13s2 ◽  
pp. CIN.S13777 ◽  
Author(s):  
Zheng Chang ◽  
Zhenjia Wang ◽  
Cody Ashby ◽  
Chuan Zhou ◽  
Guojun Li ◽  
...  

Identifying clinically relevant subtypes of a cancer using gene expression data is a challenging and important problem in medicine, and is a necessary premise to provide specific and efficient treatments for patients of different subtypes. Matrix factorization provides a solution by finding checkerboard patterns in the matrices of gene expression data. In the context of gene expression profiles of cancer patients, these checkerboard patterns correspond to genes that are up- or down-regulated in patients with particular cancer subtypes. Recently, a new matrix factorization framework for biclustering called Maximum Block Improvement (MBI) is proposed; however, it still suffers several problems when applied to cancer gene expression data analysis. In this study, we developed many effective strategies to improve MBI and designed a new program called enhanced MBI (eMBI), which is more effective and efficient to identify cancer subtypes. Our tests on several gene expression profiling datasets of cancer patients consistently indicate that eMBI achieves significant improvements in comparison with MBI, in terms of cancer subtype prediction accuracy, robustness, and running time. In addition, the performance of eMBI is much better than another widely used matrix factorization method called nonnegative matrix factorization (NMF) and the method of hierarchical clustering, which is often the first choice of clinical analysts in practice.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sooyoun Oh ◽  
Haesun Park ◽  
Xiuwei Zhang

Advances in single cell transcriptomics have allowed us to study the identity of single cells. This has led to the discovery of new cell types and high resolution tissue maps of them. Technologies that measure multiple modalities of such data add more detail, but they also complicate data integration. We offer an integrated analysis of the spatial location and gene expression profiles of cells to determine their identity. We propose scHybridNMF (single-cell Hybrid Nonnegative Matrix Factorization), which performs cell type identification by combining sparse nonnegative matrix factorization (sparse NMF) with k-means clustering to cluster high-dimensional gene expression and low-dimensional location data. We show that, under multiple scenarios, including the cases where there is a small number of genes profiled and the location data is noisy, scHybridNMF outperforms sparse NMF, k-means, and an existing method that uses a hidden Markov random field to encode cell location and gene expression data for cell type identification.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kaisong Bai ◽  
Tong Zhao ◽  
Yilong Li ◽  
Xinjian Li ◽  
Zhantian Zhang ◽  
...  

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients’ survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jing Wu ◽  
Bin Chen ◽  
Tao Han

Nonnegative matrix factorization (NMF) is a popular method for the multivariate analysis of nonnegative data. It involves decomposing a data matrix into a product of two factor matrices with all entries restricted to being nonnegative. Orthogonal nonnegative matrix factorization (ONMF) has been introduced recently. This method has demonstrated remarkable performance in clustering tasks, such as gene expression classification. In this study, we introduce two convergence methods for solving ONMF. First, we design a convergent orthogonal algorithm based on the Lagrange multiplier method. Second, we propose an approach that is based on the alternating direction method. Finally, we demonstrate that the two proposed approaches tend to deliver higher-quality solutions and perform better in clustering tasks compared with a state-of-the-art ONMF.


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