Journal Article
. 2015 Aug; 8:54.
doi: 10.1186/s12920-015-0129-6.

Development and verification of the PAM50-based Prosigna breast cancer gene signature assay

Brett Wallden 1 James Storhoff 2 Torsten Nielsen 3 Naeem Dowidar 4 Carl Schaper 5 Sean Ferree 6 Shuzhen Liu 7 Samuel Leung 8 Gary Geiss 9 Jacqueline Snider 10 Tammi Vickery 11 Sherri R Davies 12 Elaine R Mardis 13 Michael Gnant 14 Ivana Sestak 15 Matthew J Ellis 16 Charles M Perou 17 Philip S Bernard 18 Joel S Parker 19 
Affiliations
  • PMID: 26297356
  •     52 References
  •     127 citations

Abstract

Background: The four intrinsic subtypes of breast cancer, defined by differential expression of 50 genes (PAM50), have been shown to be predictive of risk of recurrence and benefit of hormonal therapy and chemotherapy. Here we describe the development of Prosigna™, a PAM50-based subtype classifier and risk model on the NanoString nCounter Dx Analysis System intended for decentralized testing in clinical laboratories.

Methods: 514 formalin-fixed, paraffin-embedded (FFPE) breast cancer patient samples were used to train prototypical centroids for each of the intrinsic subtypes of breast cancer on the NanoString platform. Hierarchical cluster analysis of gene expression data was used to identify the prototypical centroids defined in previous PAM50 algorithm training exercises. 304 FFPE patient samples from a well annotated clinical cohort in the absence of adjuvant systemic therapy were then used to train a subtype-based risk model (i.e. Prosigna ROR score). 232 samples from a tamoxifen-treated patient cohort were used to verify the prognostic accuracy of the algorithm prior to initiating clinical validation studies.

Results: The gene expression profiles of each of the four Prosigna subtype centroids were consistent with those previously published using the PCR-based PAM50 method. Similar to previously published classifiers, tumor samples classified as Luminal A by Prosigna had the best prognosis compared to samples classified as one of the three higher-risk tumor subtypes. The Prosigna Risk of Recurrence (ROR) score model was verified to be significantly associated with prognosis as a continuous variable and to add significant information over both commonly available IHC markers and Adjuvant! Online.

Conclusions: The results from the training and verification data sets show that the FDA-cleared and CE marked Prosigna test provides an accurate estimate of the risk of distant recurrence in hormone receptor positive breast cancer and is also capable of identifying a tumor's intrinsic subtype that is consistent with the previously published PCR-based PAM50 assay. Subsequent analytical and clinical validation studies confirm the clinical accuracy and technical precision of the Prosigna PAM50 assay in a decentralized setting.

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Cancer Epidemiol Biomarkers Prev, 2019 Jun 13; 28(9). PMID: 31186261    Free PMC article.
Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies.
John Svaren, John J Moran, +8 authors, Michael E Shy.
Ann Neurol, 2019 Apr 05; 85(6). PMID: 30945774    Free PMC article.
Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes.
Chanthirika Ragulan, Katherine Eason, +17 authors, Anguraj Sadanandam.
Sci Rep, 2019 May 23; 9(1). PMID: 31113981    Free PMC article.
Overexpression and alternative splicing of NF-YA in breast cancer.
Diletta Dolfini, Valentina Andrioletti, Roberto Mantovani.
Sci Rep, 2019 Sep 12; 9(1). PMID: 31506469    Free PMC article.
Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.
Andrew Tutt, Holly Tovey, +35 authors, Judith M Bliss.
Nat Med, 2018 May 02; 24(5). PMID: 29713086    Free PMC article.
Highly Cited.
The Prosigna 50-gene profile and responsiveness to adjuvant anthracycline-based chemotherapy in high-risk breast cancer patients.
Maj-Britt Jensen, Anne-Vibeke Lænkholm, +9 authors, Bent Ejlertsen.
NPJ Breast Cancer, 2020 Mar 07; 6. PMID: 32140564    Free PMC article.
A Human Adult Stem Cell Signature Marks Aggressive Variants across Epithelial Cancers.
Bryan A Smith, Nikolas G Balanis, +8 authors, Thomas G Graeber.
Cell Rep, 2018 Sep 21; 24(12). PMID: 30232014    Free PMC article.
A Gene Expression Classifier from Whole Blood Distinguishes Benign from Malignant Lung Nodules Detected by Low-Dose CT.
Andrew V Kossenkov, Rehman Qureshi, +18 authors, Louise C Showe.
Cancer Res, 2018 Nov 30; 79(1). PMID: 30487137    Free PMC article.
Pan-cancer analysis of transcriptional metabolic dysregulation using The Cancer Genome Atlas.
S R Rosario, M D Long, +3 authors, D J Smiraglia.
Nat Commun, 2018 Dec 16; 9(1). PMID: 30552315    Free PMC article.
Highly Cited.
PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts.
Kevin H Kensler, Venkat N Sankar, +13 authors, Yujing J Heng.
Cancer Epidemiol Biomarkers Prev, 2018 Dec 29; 28(4). PMID: 30591591    Free PMC article.
Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors.
Jeffrey M Conroy, Sarabjot Pabla, +37 authors, Carl Morrison.
J Immunother Cancer, 2019 Jan 27; 7(1). PMID: 30678715    Free PMC article.
Integrating Germline and Somatic Mutation Information for the Discovery of Biomarkers in Triple-Negative Breast Cancer.
Jiande Wu, Tarun Karthik Kumar Mamidi, Lu Zhang, Chindo Hicks.
Int J Environ Res Public Health, 2019 Mar 27; 16(6). PMID: 30909550    Free PMC article.
Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer.
Mustapha Abubakar, Jonine Figueroa, +8 authors, Paul D Pharoah.
Mod Pathol, 2019 Apr 13; 32(9). PMID: 30976105    Free PMC article.
A new normalization for Nanostring nCounter gene expression data.
Ramyar Molania, Johann A Gagnon-Bartsch, Alexander Dobrovic, Terence P Speed.
Nucleic Acids Res, 2019 May 23; 47(12). PMID: 31114909    Free PMC article.
On-treatment biomarkers can improve prediction of response to neoadjuvant chemotherapy in breast cancer.
Richard J Bownes, Arran K Turnbull, +3 authors, Olga Oikonomidou.
Breast Cancer Res, 2019 Jun 16; 21(1). PMID: 31200764    Free PMC article.
GAIL: An interactive webserver for inference and dynamic visualization of gene-gene associations based on gene ontology guided mining of biomedical literature.
Daniel Couch, Zhenning Yu, +8 authors, Dongjun Chung.
PLoS One, 2019 Jul 02; 14(7). PMID: 31260503    Free PMC article.
Landscape of transcriptomic interactions between breast cancer and its microenvironment.
Natalie S Fox, Syed Haider, Adrian L Harris, Paul C Boutros.
Nat Commun, 2019 Jul 17; 10(1). PMID: 31308365    Free PMC article.
Acquisition of Invasiveness by Breast Adenocarcinoma Cells Engages Established Hallmarks and Novel Regulatory Mechanisms.
Hanaa Mousa, Mahmoud Elgamal, +3 authors, Serhiy Souchelnytskyi.
Cancer Genomics Proteomics, 2019 Oct 30; 16(6). PMID: 31659104    Free PMC article.
A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer.
Rachel L Stewart, Katherine L Updike, +4 authors, Katherine E Varley.
Cancer Res, 2019 May 03; 79(13). PMID: 31048497    Free PMC article.
Refinement of breast cancer molecular classification by miRNA expression profiles.
Rolf Søkilde, Helena Persson, +11 authors, Carlos Rovira.
BMC Genomics, 2019 Jun 19; 20(1). PMID: 31208318    Free PMC article.
Ductal Carcinoma In Situ Progression in Dog Model of Breast Cancer.
Sulma I Mohammed, Sagar Utturkar, +7 authors, Margaret A Miller.
Cancers (Basel), 2020 Feb 15; 12(2). PMID: 32053966    Free PMC article.
The orphan nuclear receptor estrogen-related receptor beta (ERRβ) in triple-negative breast cancer.
Aileen I Fernandez, Xue Geng, +9 authors, Rebecca B Riggins.
Breast Cancer Res Treat, 2019 Nov 20; 179(3). PMID: 31741180    Free PMC article.
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments.
Ugo Testa, Germana Castelli, Elvira Pelosi.
Med Sci (Basel), 2020 Mar 27; 8(1). PMID: 32210163    Free PMC article.
Review.
RDGN-based predictive model for the prognosis of breast cancer.
Bing Dong, Ming Yi, +2 authors, Kongming Wu.
Exp Hematol Oncol, 2020 Jun 19; 9. PMID: 32550045    Free PMC article.
Molecular determinants of drug response in TNBC cell lines.
Nathan M Merrill, Eric J Lachacz, +7 authors, Matthew B Soellner.
Breast Cancer Res Treat, 2019 Oct 28; 179(2). PMID: 31655920    Free PMC article.
A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer.
Claire Bonneau, Antoine Eliès, +9 authors, Fatima Mechta-Grigoriou.
Breast Cancer Res, 2020 Jul 16; 22(1). PMID: 32665033    Free PMC article.
Nodal positivity decreases with age in women with early-stage, hormone receptor-positive breast cancer.
Stephanie M Downs-Canner, Charles E Gaber, +4 authors, David W Ollila.
Cancer, 2019 Dec 21; 126(6). PMID: 31860136    Free PMC article.
Unraveling the Genomic-Epigenomic Interaction Landscape in Triple Negative and Non-Triple Negative Breast Cancer.
Jiande Wu, Tarun Karthik Kumar Mamidi, Lu Zhang, Chindo Hicks.
Cancers (Basel), 2020 Jun 18; 12(6). PMID: 32545594    Free PMC article.
Delineation of the Germline and Somatic Mutation Interaction Landscape in Triple-Negative and Non-Triple-Negative Breast Cancer.
Jiande Wu, Tarun K K Mamidi, Lu Zhang, Chindo Hicks.
Int J Genomics, 2020 Jul 30; 2020. PMID: 32724790    Free PMC article.
Overview of Breast Cancer and Implications of Overtreatment of Early-Stage Breast Cancer: An Indian Perspective.
Gouri Shankar Bhattacharyya, Dinesh C Doval, +3 authors, S P Somashekhar.
JCO Glob Oncol, 2020 Jun 09; 6. PMID: 32511068    Free PMC article.
Machine learning for RNA sequencing-based intrinsic subtyping of breast cancer.
Silvia Cascianelli, Ivan Molineris, +2 authors, Enzo Medico.
Sci Rep, 2020 Aug 23; 10(1). PMID: 32826944    Free PMC article.
FGFR4 regulates tumor subtype differentiation in luminal breast cancer and metastatic disease.
Susana Garcia-Recio, Aatish Thennavan, +22 authors, Charles M Perou.
J Clin Invest, 2020 Jun 24; 130(9). PMID: 32573490    Free PMC article.
Computational approaches to support comparative analysis of multiparametric tests: Modelling versus Training.
John M S Bartlett, Jane Bayani, +8 authors, OPTIMA Trial Management Group.
PLoS One, 2020 Sep 04; 15(9). PMID: 32881987    Free PMC article.
Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer.
Taru A Muranen, Sofia Khan, +41 authors, Heli Nevanlinna.
NPJ Breast Cancer, 2020 Sep 24; 6. PMID: 32964118    Free PMC article.
Quadruple Negative Breast Cancers (QNBC) Demonstrate Subtype Consistency among Primary and Recurrent or Metastatic Breast Cancer.
Anusha Angajala, Essynce Mothershed, +5 authors, Clayton Yates.
Transl Oncol, 2018 Dec 30; 12(3). PMID: 30594038    Free PMC article.
Profiling of Invasive Breast Carcinoma Circulating Tumour Cells-Are We Ready for the 'Liquid' Revolution?
Marcin Braun, Aleksandra Markiewicz, +2 authors, Hanna Romańska.
Cancers (Basel), 2019 Jan 30; 11(2). PMID: 30691008    Free PMC article.
Review.
Should a Multigene Signature be Used in all Luminal Early Breast Cancers.
Nawale Hajjaji, Yves Marie Robin, Jacques Bonneterre.
Front Oncol, 2019 Jun 20; 9. PMID: 31214499    Free PMC article.
BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening.
Rachel G Grashow, Vanessa Y De La Rosa, +2 authors, Ruthann A Rudel.
Comput Toxicol, 2018 Feb 01; 5. PMID: 31218268    Free PMC article.
The Oncotype Dx Assay in ER-Positive, HER2-Negative Breast Cancer Patients: A Real Life Experience from a Single Cancer Center.
Stephane Thibodeau, Ioannis A Voutsadakis.
Eur J Breast Health, 2019 Jul 18; 15(3). PMID: 31312792    Free PMC article.
Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).
Aline Talhouk, Joshy George, +122 authors, Michael S Anglesio.
Clin Cancer Res, 2020 Jun 20; 26(20). PMID: 32554541    Free PMC article.
A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy.
Ziteng Li, Siyuan Chen, +8 authors, Xiaodong Zhu.
EBioMedicine, 2020 Nov 09; 62. PMID: 33161227    Free PMC article.
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes.
Dong Gui Hu, Peter I Mackenzie, +2 authors, Robyn Meech.
Cancers (Basel), 2020 Nov 19; 12(11). PMID: 33202946    Free PMC article.
Mutational signatures and mutable motifs in cancer genomes.
Igor B Rogozin, Youri I Pavlov, +5 authors, David N Cooper.
Brief Bioinform, 2017 May 13; 19(6). PMID: 28498882    Free PMC article.
Review.
Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals.
Małgorzata Szostakowska, Alicja Trębińska-Stryjewska, Ewa Anna Grzybowska, Anna Fabisiewicz.
Breast Cancer Res Treat, 2018 Nov 02; 173(3). PMID: 30382472    Free PMC article.
Review.
Quantification of intrinsic subtype ambiguity in Luminal A breast cancer and its relationship to clinical outcomes.
Neeraj Kumar, Dan Zhao, +2 authors, Peter H Gann.
BMC Cancer, 2019 Mar 10; 19(1). PMID: 30849944    Free PMC article.
Analytical validation of CanAssist-Breast: an immunohistochemistry based prognostic test for hormone receptor positive breast cancer patients.
Arun Kumar Attuluri, Chandra Prakash V Serkad, +9 authors, Manjiri M Bakre.
BMC Cancer, 2019 Mar 22; 19(1). PMID: 30894144    Free PMC article.
Characterization of molecular scores and gene expression signatures in primary breast cancer, local recurrences and brain metastases.
Mariana Bustamante Eduardo, Vlad Popovici, +5 authors, Rolf Jaggi.
BMC Cancer, 2019 Jun 09; 19(1). PMID: 31174485    Free PMC article.
Hormonal modulation of ESR1 mutant metastasis.
Guowei Gu, Lin Tian, +28 authors, Suzanne A W Fuqua.
Oncogene, 2020 Dec 17; 40(5). PMID: 33323970    Free PMC article.
An Improved, Assay Platform Agnostic, Absolute Single Sample Breast Cancer Subtype Classifier.
Mi-Kyoung Seo, Soonmyung Paik, Sangwoo Kim.
Cancers (Basel), 2020 Dec 02; 12(12). PMID: 33255759    Free PMC article.
MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression.
Kung-Chi Chang, Sarah D Diermeier, +11 authors, David L Spector.
Nat Commun, 2020 Dec 24; 11(1). PMID: 33353933    Free PMC article.
Development and validation of a NanoString BASE47 bladder cancer gene classifier.
Jordan Kardos, Tracy L Rose, +7 authors, William Y Kim.
PLoS One, 2020 Dec 18; 15(12). PMID: 33332422    Free PMC article.
Invasive lobular carcinoma of the breast: the increasing importance of this special subtype.
Amy E McCart Reed, Lauren Kalinowski, Peter T Simpson, Sunil R Lakhani.
Breast Cancer Res, 2021 Jan 09; 23(1). PMID: 33413533    Free PMC article.
Review.
Triple Negative Breast Cancer: A Review of Present and Future Diagnostic Modalities.
Sylvia Annabel Dass, Kim Liu Tan, +5 authors, Venugopal Balakrishnan.
Medicina (Kaunas), 2021 Jan 16; 57(1). PMID: 33445543    Free PMC article.
Review.
Autophagy is associated with a robust specific transcriptional signature in breast cancer subtypes.
Céline Grandvallet, Jean Paul Feugeas, +5 authors, Paul Peixoto.
Genes Cancer, 2021 Jan 26; 11(3-4). PMID: 33488952    Free PMC article.
Molecular downstaging: a new paradigm for neoadjuvant endocrine therapy.
Emanuela Ferraro, Monica N Fornier.
Ann Transl Med, 2021 Jan 26; 8(24). PMID: 33490206    Free PMC article.
Significance of Oncotype DX 21-Gene Test and Expression of Long Non-Coding RNA MALAT1 in Early and Estrogen Receptor-Positive Breast Cancer Patients.
Zhen Huang, Qinghong Qin, +4 authors, Qinguo Mo.
Cancer Manag Res, 2021 Feb 02; 13. PMID: 33519238    Free PMC article.
Retrospective Validation of a 168-Gene Expression Signature for Glioma Classification on a Single Molecule Counting Platform.
Paul Minh Huy Tran, Lynn Kim Hoang Tran, +8 authors, Jin Xiong She.
Cancers (Basel), 2021 Jan 29; 13(3). PMID: 33503830    Free PMC article.
Current Achievements and Applications of Transcriptomics in Personalized Cancer Medicine.
Stanislaw Supplitt, Pawel Karpinski, Maria Sasiadek, Izabela Laczmanska.
Int J Mol Sci, 2021 Feb 13; 22(3). PMID: 33572595    Free PMC article.
Review.
A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling.
Ainhoa Arana Echarri, Mark Beresford, +6 authors, James E Turner.
Front Immunol, 2021 Feb 19; 11. PMID: 33597950    Free PMC article.
Review.
bc-GenExMiner 4.5: new mining module computes breast cancer differential gene expression analyses.
Pascal Jézéquel, Wilfried Gouraud, +4 authors, Mario Campone.
Database (Oxford), 2021 Feb 19; 2021. PMID: 33599248    Free PMC article.
Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer.
Christen A Khella, Gaurav A Mehta, Rushabh N Mehta, Michael L Gatza.
J Pers Med, 2021 Mar 07; 11(2). PMID: 33669749    Free PMC article.
Review.
Correlation of immune infiltration with clinical outcomes in breast cancer patients: The 25-gene prognostic signatures model.
Yushan Liu, Wenfen Fu, +3 authors, Chuangui Song.
Cancer Med, 2021 Feb 25; 10(6). PMID: 33626234    Free PMC article.
Extensive analysis of the molecular biomarkers excision repair cross complementing 1, ribonucleotide reductase M1, β-tubulin III, thymidylate synthetase, and topoisomerase IIα in breast cancer: Association with clinicopathological characteristics.
Juncheng Li, Peng Sun, +3 authors, Gang Xue.
Medicine (Baltimore), 2021 Apr 10; 100(14). PMID: 33832110    Free PMC article.
Characterizing advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive analytics.
Allen Li, Jamie M Keck, +15 authors, Zahi I Mitri.
NPJ Precis Oncol, 2021 Mar 28; 5(1). PMID: 33772089    Free PMC article.
Predicting tumor response to drugs based on gene-expression biomarkers of sensitivity learned from cancer cell lines.
Yuanyuan Li, David M Umbach, +3 authors, Leping Li.
BMC Genomics, 2021 Apr 17; 22(1). PMID: 33858332    Free PMC article.
Molecular Drivers of Oncotype DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC Study.
Richard Buus, Ivana Sestak, +6 authors, Mitch Dowsett.
J Clin Oncol, 2020 Oct 28; 39(2). PMID: 33108242    Free PMC article.
DeCompress: tissue compartment deconvolution of targeted mRNA expression panels using compressed sensing.
Arjun Bhattacharya, Alina M Hamilton, Melissa A Troester, Michael I Love.
Nucleic Acids Res, 2021 Feb 02; 49(8). PMID: 33524140    Free PMC article.
Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression.
Benedetta Pellegrino, Zuzana Hlavata, +5 authors, Cinzia Solinas.
Mol Diagn Ther, 2021 May 12; 25(4). PMID: 33974235    Free PMC article.
Review.
Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy.
Shea P Connell, Robert Mills, +5 authors, The Movember Gap Urine Biomarker Consortium.
Cancers (Basel), 2021 May 01; 13(9). PMID: 33925381    Free PMC article.
Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer.
Alessia Vignoli, Emanuela Risi, +6 authors, Leonardo Tenori.
Int J Mol Sci, 2021 May 01; 22(9). PMID: 33925233    Free PMC article.
Review.
An approach for normalization and quality control for NanoString RNA expression data.
Arjun Bhattacharya, Alina M Hamilton, +5 authors, Michael I Love.
Brief Bioinform, 2020 Aug 14; 22(3). PMID: 32789507    Free PMC article.
A Systemic Inflammation Response Score for Prognostic Prediction of Breast Cancer Patients Undergoing Surgery.
Kaiming Zhang, Liqin Ping, +2 authors, Xiangsheng Xiao.
J Pers Med, 2021 Jun 03; 11(5). PMID: 34069272    Free PMC article.
The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers.
Leticia De Mattos-Arruda, Javier Cortes, +17 authors, Carlos Caldas.
NPJ Breast Cancer, 2021 Jun 09; 7(1). PMID: 34099718    Free PMC article.
High-Throughput NanoString Analysis of Oncogenic Human Papillomavirus and Tumor Microenvironment Transcription in Head and Neck Squamous Cell Carcinoma.
Wesley H Stepp.
Curr Protoc, 2021 May 26; 1(5). PMID: 34033698    Free PMC article.
INSTIGO Trial: Evaluation of a Plasma Protein Profile as a Predictive Biomarker for Metastatic Relapse of Triple Negative Breast Cancer.
Hugo Veyssière, Sejdi Lusho, +6 authors, Xavier Durando.
Front Oncol, 2021 Jul 13; 11. PMID: 34249690    Free PMC article.
Uncovering the Subtype-Specific Molecular Characteristics of Breast Cancer by Multiomics Analysis of Prognosis-Associated Genes, Driver Genes, Signaling Pathways, and Immune Activity.
Xinhui Li, Jian Zhou, +11 authors, Jing Tang.
Front Cell Dev Biol, 2021 Jul 20; 9. PMID: 34277633    Free PMC article.
Kinectin 1 promotes the growth of triple-negative breast cancer via directly co-activating NF-kappaB/p65 and enhancing its transcriptional activity.
Lin Gao, Shanze Chen, +13 authors, Chang Zou.
Signal Transduct Target Ther, 2021 Jul 06; 6(1). PMID: 34219129    Free PMC article.
DysPIA: A Novel Dysregulated Pathway Identification Analysis Method.
Limei Wang, Weixin Xie, +4 authors, Jin Li.
Front Genet, 2021 Jul 23; 12. PMID: 34290733    Free PMC article.