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Integrative Analysis Identifies Candidate Tumor Microenvironment and Intracellular Signaling Pathways that Define Tumor Heterogeneity in NF1

1
Computational Oncology, Sage Bionetworks, Seattle, WA 98121, USA
2
Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Philadelphia, PA 19102, USA
3
Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI 53715, USA
4
Morgridge Institute for Research, Madison, WI 53715, USA
5
Division of Oncology, Washington University Medical School, St. Louis, MO 63110, USA
6
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
7
Neurology, Neurosurgery and Oncology, Johns Hopkins University, Baltimore, MD 21287, USA
8
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
These authors have equal contribution.
Genes 2020, 11(2), 226; https://doi.org/10.3390/genes11020226
Received: 15 January 2020 / Revised: 15 February 2020 / Accepted: 19 February 2020 / Published: 21 February 2020
(This article belongs to the Special Issue Genomics and Models of Nerve Sheath Tumors)
Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40–60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions. View Full-Text
Keywords: neurofibromatosis type 1; nerve sheath tumor; cancer; latent variables; machine learning; supervised learning; transfer learning; random forest; metaVIPER; tumor deconvolution neurofibromatosis type 1; nerve sheath tumor; cancer; latent variables; machine learning; supervised learning; transfer learning; random forest; metaVIPER; tumor deconvolution
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MDPI and ACS Style

Banerjee, J.; Allaway, R.J.; Taroni, J.N.; Baker, A.; Zhang, X.; Moon, C.I.; Pratilas, C.A.; Blakeley, J.O.; Guinney, J.; Hirbe, A.; Greene, C.S.; Gosline, S.J. Integrative Analysis Identifies Candidate Tumor Microenvironment and Intracellular Signaling Pathways that Define Tumor Heterogeneity in NF1. Genes 2020, 11, 226. https://doi.org/10.3390/genes11020226

AMA Style

Banerjee J, Allaway RJ, Taroni JN, Baker A, Zhang X, Moon CI, Pratilas CA, Blakeley JO, Guinney J, Hirbe A, Greene CS, Gosline SJ. Integrative Analysis Identifies Candidate Tumor Microenvironment and Intracellular Signaling Pathways that Define Tumor Heterogeneity in NF1. Genes. 2020; 11(2):226. https://doi.org/10.3390/genes11020226

Chicago/Turabian Style

Banerjee, Jineta; Allaway, Robert J.; Taroni, Jaclyn N.; Baker, Aaron; Zhang, Xiaochun; Moon, Chang I.; Pratilas, Christine A.; Blakeley, Jaishri O.; Guinney, Justin; Hirbe, Angela; Greene, Casey S.; Gosline, Sara J. 2020. "Integrative Analysis Identifies Candidate Tumor Microenvironment and Intracellular Signaling Pathways that Define Tumor Heterogeneity in NF1" Genes 11, no. 2: 226. https://doi.org/10.3390/genes11020226

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