title: In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development.
abstract: Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy.
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Ozerov
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Lezhnina
authors.affiliation: The Johns Hopkins University, School of Medicine, Department of Otolaryngology, Head and Neck Cancer Research, 1550 Orleans Street, Baltimore, Maryland 21231, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Izumchenko
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.
authors.forename: Artem V
authors.initials: AV
authors.lastname: Artemov
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Medintsev
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Vanhaelen
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.|Laboratory of Bioinformatics, D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, Moscow 117997, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Aliper
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.|Laboratory of Bioinformatics, D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, Moscow 117997, Russia.
authors.forename: Andreyan N
authors.initials: AN
authors.lastname: Osipov
authors.affiliation: BioTime, Inc., 1010 Atlantic Avenue, Alameda, California 94501, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Labat
authors.affiliation: BioTime, Inc., 1010 Atlantic Avenue, Alameda, California 94501, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: West
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.|Laboratory of Bioinformatics, D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, Moscow 117997, Russia.|National Research Centre 'Kurchatov Institute', Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies, 1, Akademika Kurchatova square, Moscow 123182, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Buzdin
authors.affiliation: Boston University, Department of Biomedical Engineering, 44 Cummington Street, Boston, Massachusetts 02215, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.|Skolkovo Foundation, 5 Nobelya street, Skolkovo Innovation Centre, Mozhajskij region, Moscow 143026, Russia.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.|Laboratory of Bioinformatics, D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, Moscow 117997, Russia.|National Research Centre 'Kurchatov Institute', Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies, 1, Akademika Kurchatova square, Moscow 123182, Russia.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Borisov
authors.affiliation: Nutrition and Metabolic Health group, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
authors.forename: Irina
authors.initials: I
authors.lastname: Irincheeva
authors.affiliation: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Khokhlovich
authors.affiliation: The Johns Hopkins University, School of Medicine, Department of Otolaryngology, Head and Neck Cancer Research, 1550 Orleans Street, Baltimore, Maryland 21231, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.affiliation: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Miguel Luiz
authors.initials: ML
authors.lastname: Camargo
authors.affiliation: Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, B301, 1101 33rd Street, Baltimore, Maryland 21218, USA.|Laboratory of Bioinformatics, D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, Moscow 117997, Russia.|The Biogerontology Research Foundation, 2354 Chynoweth House, Trevissome Park, Truro TR4 8UN, UK.
authors.forename: Alex
authors.identifier: 0000-0001-7067-8966
authors.initials: A
authors.lastname: Zhavoronkov
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D003198:Computer Simulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008954:Models, Biological; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D012372:ROC Curve; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers; D017239:Paclitaxel