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Tumor Copy Number Deconvolution Integrating Bulk and Single-Cell Sequencing Data: Supplementary Materials [article]

Haoyun Lei, Bochuan Lyu, E. Michael Gertz, Alejandro A. Schaeffer, Xulian Shi, Kui Wu, Guibo Li, Liquin Xu, Yong Hu, Michael Dean, Russell Schwartz
2019 bioRxiv   pre-print
We have developed strategies for deconvolution and tumor phylogenetics combining limited amounts of bulk and single-cell data to gain some advantages of single-cell resolution with much lower cost, with  ...  specific focus on deconvolving genomic copy number data.  ...  It . doi: bioRxiv preprint Bulk and Single-Cell Copy Number Deconvolution 13 Fig. 8 .  ... 
doi:10.1101/519892 fatcat:radxvlu7hndk3lwepn2a22xxkq

Tumor heterogeneity assessed by sequencing and fluorescence in situ hybridization (FISH) data [article]

Haoyun Lei, E. Michael Gertz, Alejandro A. Schäffer, Xuecong Fu, Yifeng Tao, Kerstin Heselmeyer-Haddad, Irianna Torres, Xulian Shi, Kui Wu, Guibo Li, Liqin Xu, Yong Hou (+3 others)
2020 bioRxiv   pre-print
Analysis of real glioblastoma data for which FISH, bulk sequence, and single cell sequence are all available confirms the power of FISH to enhance accurate reconstruction of clonal copy number evolution  ...  in conjunction with bulk and optionally single-cell sequence  ...  of Cancer Epidemiology and Genetics  ... 
doi:10.1101/2020.02.29.970392 fatcat:fkxfbqvdkncvbac2fp7l4pnoe4

Clinical Perspectives of Single-Cell RNA Sequencing

Nayoung Kim, Hye Hyeon Eum, Hae-Ock Lee
2021 Biomolecules  
The results obtained upon employing bulk cancer genomics indicate that single-cell genomics is at an early stage with respect to exploration of clinical relevance and requires further innovations to become  ...  The ability of single-cell genomics to resolve cellular heterogeneity is highly appreciated in cancer and is being exploited for precision medicine.  ...  Acknowledgments: Discussion and technical comments from Areum Jo and Dasom Jeong (The  ... 
doi:10.3390/biom11081161 pmid:34439827 pmcid:PMC8394304 fatcat:mba6asurhvcnxjy3xr42yz76fe

Tracing the evolution of aneuploid cancers by multiregional sequencing with CRUST

Subhayan Chattopadhyay, Jenny Karlsson, Anders Valind, Natalie Andersson, David Gisselsson
2021 Briefings in Bioinformatics  
Absent à priori copy number data, it renders in silico copy number estimations from bulk sequences.  ...  Two limiting factors for clonal deconvolution that have remained unresolved are variation in purity and chromosomal copy number across different samples of the same tumor.  ...  Council, and Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure.  ... 
doi:10.1093/bib/bbab292 pmid:34343239 pmcid:PMC8981300 fatcat:vgjspskpu5aj3and6dr4ynsboe

An assessment of computational methods for estimating purity and clonality using genomic data derived from heterogeneous tumor tissue samples

V. K. Yadav, S. De
2014 Briefings in Bioinformatics  
If properly used, these tools have potentials to complement single-cell genomics and immunoFISH analyses, and provide novel insights into tumor heterogeneity.  ...  Solid tumor samples typically contain multiple distinct clonal populations of cancer cells, and also stromal and immune cell contamination.  ...  The comparative analysis results published here are in part based upon data generated by The Cancer Genome Atlas pilot project [56] established by the NCI and NHGRI (dbGAP accession ID: phs000178.v8.  ... 
doi:10.1093/bib/bbu002 pmid:24562872 pmcid:PMC4794615 fatcat:mcg7fqdg65gbhnc7okknmpz774

Tracing the evolution of aneuploid cancers from multiregional sequencing [article]

Subhayan Chattopadhyay, Jenny Karlsson, Anders Valind, Natalie Andersson, David Gisselsson
2020 bioRxiv   pre-print
We present a semi-supervised algorithm that normalizes for purity and incorporates allelic composition with bulk sequencing to reliably segregate clonal/subclonal variants even at low sequencing depth  ...  However, the frequencies of mutated alleles are often distorted by variation in copy number of mutated loci as well as the purity across samples.  ...  Council, and Uppsala Multidisciplinary Center for Advanced (which was not certified by peer review) is the author/funder.  ... 
doi:10.1101/2020.11.11.376467 fatcat:5jg7bp6u7nfunfjwjr54s7cg2y

Exploring Additional Valuable Information From Single-Cell RNA-Seq Data

Yunjin Li, Qiyue Xu, Duojiao Wu, Geng Chen
2020 Frontiers in Cell and Developmental Biology  
Additionally, we survey the integration of single-cell and bulk RNA-seq datasets for deconvoluting the cell composition of large-scale bulk samples and linking single-cell signatures to patient outcomes  ...  Here, we first review cell-to-cell communication exploration, RNA velocity inference, identification of large-scale copy number variations and single nucleotide changes, and chromatin accessibility prediction  ...  FIGURE 6 | 6 Integration of single-cell and bulk RNA-seq data for cell-type decomposition and survival analysis.  ... 
doi:10.3389/fcell.2020.593007 pmid:33335900 pmcid:PMC7736616 fatcat:wbboyh6gjjbvxbutsmtmv53ztq

Machine learning for deciphering cell heterogeneity and gene regulation

Michael Scherer, Florian Schmidt, Olga Lazareva, Jörn Walter, Jan Baumbach, Marcel H. Schulz, Markus List
2021 Nature Computational Science  
Gene regulation on single-cell level In classical bulk sequencing, individual cell types have to be isolated a priori or deconvolution methods need to be applied to disentangle possible contributions of  ...  UnionCom and SCIM are more generic approaches that allow integrating any single cell multi-omics data: they produce a single co-embedding space from independent samples and technologies.  ...  Fernando Chirigati was the primary editor on this Review and managed its editorial process and peer review in collaboration with the rest of the editorial team.  ... 
doi:10.1038/s43588-021-00038-7 fatcat:tw77ti33bvhdboy7wafma5auey

Understanding tumor ecosystems by single-cell sequencing: promises and limitations

Xianwen Ren, Boxi Kang, Zemin Zhang
2018 Genome Biology  
Cellular heterogeneity within and across tumors has been a major obstacle in understanding and treating cancer, and the complex heterogeneity is masked if bulk tumor tissues are used for analysis.  ...  Overview of single-cell sequencing and analysis Single-cell sequencing technologies have improved considerably from the initial proof-of-principle studies [6] [7] [8] .  ...  Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.  ... 
doi:10.1186/s13059-018-1593-z fatcat:puz6d5obtjdlreiasxj2s3mxou

Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing

Yuchao Jiang, Yu Qiu, Andy J. Minn, Nancy R. Zhang
2016 Proceedings of the National Academy of Sciences of the United States of America  
Here, we propose Canopy, a method for inferring the evolutionary phylogeny of a tumor using both somatic copy number alterations and single-nucleotide alterations from one or more samples derived from  ...  Canopy is applied to bulk sequencing datasets of both longitudinal and spatial experimental designs and to a transplantable metastasis model derived from human cancer cell line MDA-MB-231.  ...  Despite its promise, single-cell DNA sequencing data are much noisier than bulk sequencing data due to allele dropout events and amplification errors (22) , and furthermore, the per-cell coverage is still  ... 
doi:10.1073/pnas.1522203113 pmid:27573852 pmcid:PMC5027458 fatcat:wge7d574pnazvcwnhcoyrxxipe

Computational approaches for inferring tumor evolution from single-cell genomic data

Hamim Zafar, Nicholas Navin, Luay Nakhleh, Ken Chen
2018 Current Opinion in Systems Biology  
Genomic heterogeneity in tumors results from mutations and selection of high-fitness single cells, the operational components of evolution.  ...  The rapidly advancing field of single-cell genomics provides an opportunity to study tumor heterogeneity and evolution at the ultimate level of resolution.  ...  Integrating bulk and single cells from the same tissue can provide complementary knowledge in such scenario.  ... 
doi:10.1016/j.coisb.2017.11.008 fatcat:ynw5xltnvndghbajgpmhnjpmhy

Intrinsic Resistance to Immune Checkpoint Blockade in a Mismatch Repair Deficient Colorectal Cancer

Carino Gurjao, David Liu, Matan Hofree, Saud H AlDubayan, Isaac Wakiro, Mei-Ju Su, Kristen Felt, Evisa Gjini, Lauren K Brais, Asaf Rotem, Michael H Rosenthal, Orit Rozenblatt-Rosen (+8 others)
2019 Cancer immunology research  
Immune infiltration deconvolution analysis of bulk transcriptome data from this anti-PD-1-resistant tumor and hundreds of other colorectal cancer specimens revealed a high natural killer cell and M2 macrophage  ...  This was confirmed by single-cell transcriptome analysis and multiplex immunofluorescence.  ...  Figure 3 : 3 NK cell infiltration in the tumor-immune microenvironment (A) Immune infiltrates deconvolution from RNA sequencing data.  ... 
doi:10.1158/2326-6066.cir-18-0683 pmid:31217164 pmcid:PMC6679789 fatcat:zrdbe2h66bgfzf2kef6k7oqqau

Single-cell RNA-seq data reveals TNBC tumor heterogeneity through characterizing subclone compositions and proportions [article]

Weida Wang, Jinyuan Xu, Shuyuan Wang, Peng Xia, Li Zhang, Lei Yu, Jie Wu, Qian Song, Bo Zhang, Chaohan Xu, Yun Xiao
2019 bioRxiv   pre-print
Here we combine single-cell and bulk sequencing data to analyze tumor heterogeneity through characterizing subclone compositions and proportions.  ...  Based on sing-cell RNA-seq data (GSE118389) we identified five distinct cell subpopulations and characterized their biological functions based on their gene markers.  ...  Anna et al. developed a novel method: Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells, and applied it to 10 early-stage breast cancer patients.  ... 
doi:10.1101/858290 fatcat:jdev76y2dnavpczyfq7767d4cm

A novel method to identify cell-type specific regulatory variants and their role in cancer risk [article]

Cynthia A Kalita, Alexander Gusev
2021 bioRxiv   pre-print
However, eQTLs are known to exert cell type specific effects, and existing methods to identify cell type specific QTLs in bulk data require large sample sizes.  ...  Results: Here, we propose DeCAF (DEconvoluted cell type Allele specific Function), a new method to identify cell-fraction (cf) QTLs in tumors by leveraging both allelic and total expression information  ...  Indeed, the earliest applications of allelic imbalance in cancer were to identify copy number changes from sequenced DNA.  ... 
doi:10.1101/2021.11.11.468278 fatcat:ufut73zokrbzpm3gv3usvfmwc4

Single-Cell Deconvolution of Head and Neck Squamous Cell Carcinoma

Zongtai Qi, Yating Liu, Michael Mints, Riley Mullins, Reilly Sample, Travis Law, Thomas Barrett, Angela L. Mazul, Ryan S. Jackson, Stephen Y. Kang, Patrik Pipkorn, Anuraag S. Parikh (+3 others)
2021 Cancers  
We leverage bulk RNA-seq data from >500 HNSCC samples profiled by The Cancer Genome Atlas (TCGA), and using single-cell data as a reference, apply two newly developed deconvolution algorithms (CIBERSORTx  ...  and MuSiC) to the bulk transcriptome data to quantitatively estimate cell-type proportions for each tumor in TCGA.  ...  Acknowledgments: The results here are in whole or part based upon data generated by the TCGA Research Network: (accessed on 1 March 2020).  ... 
doi:10.3390/cancers13061230 pmid:33799782 pmcid:PMC7999850 fatcat:hsymfuhpirh6rnxqglogjcbe7e
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