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Transcriptome Deconvolution of Heterogeneous Tumor Samples with Immune Infiltration

51 Pages Posted: 9 Jun 2018 Publication Status: Published

See all articles by Zeya Wang

Zeya Wang

University of Texas at Houston - Department of Bioinformatics and Computational Biology; Rice University - Department of Statistics

Shaolong Cao

University of Texas at Houston - Department of Bioinformatics and Computational Biology

Jeffrey Morris

University of Texas at Houston - Department of Biostatistics

Jaeil Ahn

Georgetown University - Translational Neurotherapeutics Program (TNP); Georgetown University - Department of Biostatistics, Bioinformatics and Biomathematics (DBBB)

Rongjie Liu

University of Texas at Houston - Department of Biostatistics

Svitlana Tyekucheva

Harvard University - Department of Biostatistics and Computational Biology; Harvard University - Department of Biostatistics

Fan Gao

Rice University, Jesse H. Jones Graduate School of Business, Department of Statistics

Bo Li

University of Texas at Dallas - Bioinformatics and Immunology

Wei Lu

University of Texas at Houston - Department of Translational Molecular Pathology

Ximing Tang

University of Texas at Houston - Department of Translational Molecular Pathology

Ignacio I. Wistuba

University of Texas at Houston - Department of Translational Molecular Pathology

Michaela Bowden

Harvard University - Department of Oncologic Pathology

Lorelei Mucci

Harvard University - Department of Epidemiology

Massimo Loda

Harvard University - Department of Oncologic Pathology; Harvard University - Brigham and Women's Hospital

Giovanni Parmigiani

Harvard University - Department of Biostatistics and Computational Biology; Harvard University - Department of Biostatistics

Chris C. Holmes

University of Oxford - Department of Statistics

Wenyi Wang

University of Texas at Houston - Department of Bioinformatics and Computational Biology

More...

Abstract

Transcriptomic deconvolution in cancer and other heterogeneous tissues remains challenging. Available methods lack the ability to estimate both component-specific proportions and expression profiles for individual samples. We present DeMixT, a new tool to deconvolve high dimensional data from mixtures of more than two components. DeMixT implements an iterated conditional mode algorithm and a novel gene-set-based component merging approach to improve accuracy. In a series of experimental validation studies and application to TCGA data, DeMixT showed high accuracy. Improved deconvolution is an important step towards linking tumor transcriptomic data with clinical outcomes.

Suggested Citation

Wang, Zeya and Cao, Shaolong and Morris, Jeffrey and Ahn, Jaeil and Liu, Rongjie and Tyekucheva, Svitlana and Gao, Fan and Li, Bo and Lu, Wei and Tang, Ximing and Wistuba, Ignacio I. and Bowden, Michaela and Mucci, Lorelei and Loda, Massimo and Parmigiani, Giovanni and Holmes, Chris C. and Wang, Wenyi, Transcriptome Deconvolution of Heterogeneous Tumor Samples with Immune Infiltration (2018). Available at SSRN: https://ssrn.com/abstract=3188487 or http://dx.doi.org/10.2139/ssrn.3188487
This version of the paper has not been formally peer reviewed.

Zeya Wang

University of Texas at Houston - Department of Bioinformatics and Computational Biology ( email )

1515 Holocombe Blvd
1400 Pressler St., Floor 4, FCT4.6000
Houston, TX 77030
United States

Rice University - Department of Statistics ( email )

6100 South Main Street
P.O. Box 1892
Houston, TX 77005-1892
United States

Shaolong Cao

University of Texas at Houston - Department of Bioinformatics and Computational Biology

1515 Holocombe Blvd
1400 Pressler St., Floor 4, FCT4.6000
Houston, TX 77030
United States

Jeffrey Morris

University of Texas at Houston - Department of Biostatistics ( email )

1515 Holcombe Blvd
Houston, TX 77230-1402
United States

Jaeil Ahn

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Georgetown University - Department of Biostatistics, Bioinformatics and Biomathematics (DBBB)

4000 Reservoir Rd., NW
Washington, DC
United States

Rongjie Liu

University of Texas at Houston - Department of Biostatistics ( email )

1515 Holcombe Blvd
Houston, TX 77230-1402
United States

Svitlana Tyekucheva

Harvard University - Department of Biostatistics and Computational Biology ( email )

450 Brookline Ave
Boston, MA 02215
United States

Harvard University - Department of Biostatistics ( email )

Boston, MA
United States

Fan Gao

Rice University, Jesse H. Jones Graduate School of Business, Department of Statistics

6100 South Main Street
P.O. Box 1892
Houston, TX 77005-1892
United States

Bo Li

University of Texas at Dallas - Bioinformatics and Immunology

23 Harry Hines Blvd.
Dallas, TX
United States

Wei Lu

University of Texas at Houston - Department of Translational Molecular Pathology

2130 West Holcombe Boulevard, Suite 910
Houston, TX 77030
United States

Ximing Tang

University of Texas at Houston - Department of Translational Molecular Pathology

2130 West Holcombe Boulevard, Suite 910
Houston, TX 77030
United States

Ignacio I. Wistuba

University of Texas at Houston - Department of Translational Molecular Pathology

2130 West Holcombe Boulevard, Suite 910
Houston, TX 77030
United States

Michaela Bowden

Harvard University - Department of Oncologic Pathology ( email )

450 Brookline Avenue
Boston, MA 02115
United States

Lorelei Mucci

Harvard University - Department of Epidemiology ( email )

655 Huntington Ave.
Boston, MA 02115
United States

Massimo Loda

Harvard University - Department of Oncologic Pathology ( email )

450 Brookline Avenue
Boston, MA 02115
United States

Harvard University - Brigham and Women's Hospital ( email )

75 Francis St.
Boston, MA 02115
United States

Giovanni Parmigiani

Harvard University - Department of Biostatistics and Computational Biology ( email )

450 Brookline Ave
Boston, MA 02215
United States

Harvard University - Department of Biostatistics ( email )

Boston, MA
United States

Chris C. Holmes

University of Oxford - Department of Statistics ( email )

24-29 St Giles
Oxford
United Kingdom

Wenyi Wang (Contact Author)

University of Texas at Houston - Department of Bioinformatics and Computational Biology ( email )

1515 Holocombe Blvd
1400 Pressler St., Floor 4, FCT4.6000
Houston, TX 77030
United States

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