iScience (Mar 2024)
ProteoMixture: A cell type deconvolution tool for bulk tissue proteomic data
- Pang-ning Teng,
- Joshua P. Schaaf,
- Tamara Abulez,
- Brian L. Hood,
- Katlin N. Wilson,
- Tracy J. Litzi,
- David Mitchell,
- Kelly A. Conrads,
- Allison L. Hunt,
- Victoria Olowu,
- Julie Oliver,
- Fred S. Park,
- Marshé Edwards,
- AiChun Chiang,
- Matthew D. Wilkerson,
- Praveen-Kumar Raj-Kumar,
- Christopher M. Tarney,
- Kathleen M. Darcy,
- Neil T. Phippen,
- G. Larry Maxwell,
- Thomas P. Conrads,
- Nicholas W. Bateman
Affiliations
- Pang-ning Teng
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Joshua P. Schaaf
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Tamara Abulez
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Brian L. Hood
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Katlin N. Wilson
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Tracy J. Litzi
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- David Mitchell
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Kelly A. Conrads
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Allison L. Hunt
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; Women’s Health Integrated Research Center, Women’s Service Line, Inova Health System, Falls Church, VA 22042, USA
- Victoria Olowu
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Julie Oliver
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Fred S. Park
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Marshé Edwards
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- AiChun Chiang
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA
- Matthew D. Wilkerson
- Center for Military Precision Health, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
- Praveen-Kumar Raj-Kumar
- Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA
- Christopher M. Tarney
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The John P. Murtha Cancer Center, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD 20889, USA
- Kathleen M. Darcy
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA; The John P. Murtha Cancer Center, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD 20889, USA
- Neil T. Phippen
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The John P. Murtha Cancer Center, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD 20889, USA
- G. Larry Maxwell
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; Women’s Health Integrated Research Center, Women’s Service Line, Inova Health System, Falls Church, VA 22042, USA; The John P. Murtha Cancer Center, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD 20889, USA
- Thomas P. Conrads
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; Women’s Health Integrated Research Center, Women’s Service Line, Inova Health System, Falls Church, VA 22042, USA; The John P. Murtha Cancer Center, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD 20889, USA; Corresponding author
- Nicholas W. Bateman
- Gynecologic Cancer Center of Excellence and the Women’s Health Integrated Research Center, Annandale, VA 22003, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA; The John P. Murtha Cancer Center, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD 20889, USA; Corresponding author
- Journal volume & issue
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Vol. 27,
no. 3
p. 109198
Abstract
Summary: Numerous multi-omic investigations of cancer tissue have documented varying and poor pairwise transcript:protein quantitative correlations, and most deconvolution tools aiming to predict cell type proportions (cell admixture) have been developed and credentialed using transcript-level data alone. To estimate cell admixture using protein abundance data, we analyzed proteome and transcriptome data generated from contrived admixtures of tumor, stroma, and immune cell models or those selectively harvested from the tissue microenvironment by laser microdissection from high grade serous ovarian cancer (HGSOC) tumors. Co-quantified transcripts and proteins performed similarly to estimate stroma and immune cell admixture (r ≥ 0.63) in two commonly used deconvolution algorithms, ESTIMATE or ConsensusTME. We further developed and optimized protein-based signatures estimating cell admixture proportions and benchmarked these using bulk tumor proteomic data from over 150 patients with HGSOC. The optimized protein signatures supporting cell type proportion estimates from bulk tissue proteomic data are available at https://lmdomics.org/ProteoMixture/.
