Truncated Robust Principal Component Analysis and Noise Reduction for Single Cell RNA Sequencing Data

2019 ◽  
Vol 26 (8) ◽  
pp. 782-793 ◽  
Author(s):  
Krzysztof Gogolewski ◽  
Maciej Sykulski ◽  
Neo Christopher Chung ◽  
Anna Gambin
2019 ◽  
Author(s):  
Andrea Tangherloni ◽  
Federico Ricciuti ◽  
Daniela Besozzi ◽  
Pietro Liò ◽  
Ana Cvejic

Autoencoders (AEs) have been effectively used to capture the non-linearities among gene interactions of single-cell RNA sequencing (scRNA-Seq) data. However, their integration with the common scRNA-Seq bioinformatics pipelines still poses a challenge. Here, we introduce scAEspy, a unifying tool that embodies five of the most advanced AEs and different loss functions, including two novel AEs that we developed. scAEspy allows the integration of data generated using different scRNA-Seq platforms. We benchmarked scAEspy against principal component analysis (PCA) on five public datasets, showing that our new AEs outperform the existing solutions, achieving more than 20% increase of the Rand Index in the identification of cell clusters.


Complexity ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yue Hu ◽  
Jin-Xing Liu ◽  
Ying-Lian Gao ◽  
Sheng-Jun Li ◽  
Juan Wang

In the big data era, sequencing technology has produced a large number of biological sequencing data. Different views of the cancer genome data provide sufficient complementary information to explore genetic activity. The identification of differentially expressed genes from multiview cancer gene data is of great importance in cancer diagnosis and treatment. In this paper, we propose a novel method for identifying differentially expressed genes based on tensor robust principal component analysis (TRPCA), which extends the matrix method to the processing of multiway data. To identify differentially expressed genes, the plan is carried out as follows. First, multiview data containing cancer gene expression data from different sources are prepared. Second, the original tensor is decomposed into a sum of a low-rank tensor and a sparse tensor using TRPCA. Third, the differentially expressed genes are considered to be sparse perturbed signals and then identified based on the sparse tensor. Fourth, the differentially expressed genes are evaluated using Gene Ontology and Gene Cards tools. The validity of the TRPCA method was tested using two sets of multiview data. The experimental results showed that our method is superior to the representative methods in efficiency and accuracy aspects.


Author(s):  
Cornelia Fuetterer ◽  
Thomas Augustin ◽  
Christiane Fuchs

AbstractThe analysis of single-cell RNA sequencing data is of great importance in health research. It challenges data scientists, but has enormous potential in the context of personalized medicine. The clustering of single cells aims to detect different subgroups of cell populations within a patient in a data-driven manner. Some comparison studies denote single-cell consensus clustering (SC3), proposed by Kiselev et al. (Nat Methods 14(5):483–486, 2017), as the best method for classifying single-cell RNA sequencing data. SC3 includes Laplacian eigenmaps and a principal component analysis (PCA). Our proposal of unsupervised adapted single-cell consensus clustering (adaSC3) suggests to replace the linear PCA by diffusion maps, a non-linear method that takes the transition of single cells into account. We investigate the performance of adaSC3 in terms of accuracy on the data sets of the original source of SC3 as well as in a simulation study. A comparison of adaSC3 with SC3 as well as with related algorithms based on further alternative dimension reduction techniques shows a quite convincing behavior of adaSC3.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii110-ii110
Author(s):  
Christina Jackson ◽  
Christopher Cherry ◽  
Sadhana Bom ◽  
Hao Zhang ◽  
John Choi ◽  
...  

Abstract BACKGROUND Glioma associated myeloid cells (GAMs) can be induced to adopt an immunosuppressive phenotype that can lead to inhibition of anti-tumor responses in glioblastoma (GBM). Understanding the composition and phenotypes of GAMs is essential to modulating the myeloid compartment as a therapeutic adjunct to improve anti-tumor immune response. METHODS We performed single-cell RNA-sequencing (sc-RNAseq) of 435,400 myeloid and tumor cells to identify transcriptomic and phenotypic differences in GAMs across glioma grades. We further correlated the heterogeneity of the GAM landscape with tumor cell transcriptomics to investigate interactions between GAMs and tumor cells. RESULTS sc-RNAseq revealed a diverse landscape of myeloid-lineage cells in gliomas with an increase in preponderance of bone marrow derived myeloid cells (BMDMs) with increasing tumor grade. We identified two populations of BMDMs unique to GBMs; Mac-1and Mac-2. Mac-1 demonstrates upregulation of immature myeloid gene signature and altered metabolic pathways. Mac-2 is characterized by expression of scavenger receptor MARCO. Pseudotime and RNA velocity analysis revealed the ability of Mac-1 to transition and differentiate to Mac-2 and other GAM subtypes. We further found that the presence of these two populations of BMDMs are associated with the presence of tumor cells with stem cell and mesenchymal features. Bulk RNA-sequencing data demonstrates that gene signatures of these populations are associated with worse survival in GBM. CONCLUSION We used sc-RNAseq to identify a novel population of immature BMDMs that is associated with higher glioma grades. This population exhibited altered metabolic pathways and stem-like potentials to differentiate into other GAM populations including GAMs with upregulation of immunosuppressive pathways. Our results elucidate unique interactions between BMDMs and GBM tumor cells that potentially drives GBM progression and the more aggressive mesenchymal subtype. Our discovery of these novel BMDMs have implications in new therapeutic targets in improving the efficacy of immune-based therapies in GBM.


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