BACKGROUND: An increasing number of clinical trials require biomarker-driven patient stratification, especially for revolutionary immune checkpoint blockade therapy. Due to the complicated interaction between a tumor and its microenvironment, single biomarkers, such as PDL1 protein level, tumor mutational burden (TMB), single gene mutation and expression, are far from satisfactory for response prediction or patient stratification. Recently, combinatorial biomarkers were reported to be more precise and powerful for predicting therapy response and identifying potential target populations with superior survival. However, there is a lack of dedicated tools for such combinatorial biomarker analysis. RESULTS: Here, we present dualmarker, an R package designed to facilitate the data exploration for dual biomarker combinations. Given two biomarkers, dualmarker comprehensively visualizes their association with drug response and patient survival through 14 types of plots, such as boxplots, scatterplots, ROCs, and Kaplan-Meier plots. Using logistic regression and Cox regression models, dualmarker evaluated the superiority of dual markers over single markers by comparing the data fitness of dual-marker versus single-marker models, which was utilized for de novo searching for new biomarker pairs. We demonstrated this straightforward workflow and comprehensive capability by using public biomarker data from one bladder cancer patient cohort (IMvigor210 study); we confirmed the previously reported biomarker pair TMB/TGF-beta signature and CXCL13 expression/ARID1A mutation for response and survival analyses, respectively. In addition, dualmarker de novo identified new biomarker partners, for example, in overall survival modelling, the model with combination of HMGB1 expression and ARID1A mutation had statistically better goodness-of-fit than the model with either HMGB1 or ARID1A as single marker. CONCLUSIONS: The dualmarker package is an open-source tool for the visualization and identification of combinatorial dual biomarkers. It streamlines the dual marker analysis flow into user-friendly functions and can be used for data exploration and hypothesis generation. Its code is freely available at GitHub at https://github.com/maxiaopeng/dualmarker under MIT license.
BACKGROUND: An increasing number of clinical trials require biomarker-driven patient stratification, especially for revolutionary immune checkpoint blockade therapy. Due to the complicated interaction between a tumor and its microenvironment, single biomarkers, such as PDL1 protein level, tumor mutational burden (TMB), single gene mutation and expression, are far from satisfactory for response prediction or patient stratification. Recently, combinatorial biomarkers were reported to be more precise and powerful for predicting therapy response and identifying potential target populations with superior survival. However, there is a lack of dedicated tools for such combinatorial biomarker analysis. RESULTS: Here, we present dualmarker, an R package designed to facilitate the data exploration for dual biomarker combinations. Given two biomarkers, dualmarker comprehensively visualizes their association with drug response and patient survival through 14 types of plots, such as boxplots, scatterplots, ROCs, and Kaplan-Meier plots. Using logistic regression and Cox regression models, dualmarker evaluated the superiority of dual markers over single markers by comparing the data fitness of dual-marker versus single-marker models, which was utilized for de novo searching for new biomarker pairs. We demonstrated this straightforward workflow and comprehensive capability by using public biomarker data from one bladder cancerpatient cohort (IMvigor210 study); we confirmed the previously reported biomarker pair TMB/TGF-beta signature and CXCL13 expression/ARID1A mutation for response and survival analyses, respectively. In addition, dualmarker de novo identified new biomarker partners, for example, in overall survival modelling, the model with combination of HMGB1 expression and ARID1A mutation had statistically better goodness-of-fit than the model with either HMGB1 or ARID1A as single marker. CONCLUSIONS: The dualmarker package is an open-source tool for the visualization and identification of combinatorial dual biomarkers. It streamlines the dual marker analysis flow into user-friendly functions and can be used for data exploration and hypothesis generation. Its code is freely available at GitHub at https://github.com/maxiaopeng/dualmarker under MIT license.
Entities:
Keywords:
Combinatory dual biomarker; Cox model; Logistic regression; R package
Authors: Razvan Cristescu; Robin Mogg; Mark Ayers; Andrew Albright; Erin Murphy; Jennifer Yearley; Xinwei Sher; Xiao Qiao Liu; Hongchao Lu; Michael Nebozhyn; Chunsheng Zhang; Jared K Lunceford; Andrew Joe; Jonathan Cheng; Andrea L Webber; Nageatte Ibrahim; Elizabeth R Plimack; Patrick A Ott; Tanguy Y Seiwert; Antoni Ribas; Terrill K McClanahan; Joanne E Tomassini; Andrey Loboda; David Kaufman Journal: Science Date: 2018-10-12 Impact factor: 47.728
Authors: Sanjeev Mariathasan; Shannon J Turley; Dorothee Nickles; Alessandra Castiglioni; Kobe Yuen; Yulei Wang; Edward E Kadel; Hartmut Koeppen; Jillian L Astarita; Rafael Cubas; Suchit Jhunjhunwala; Romain Banchereau; Yagai Yang; Yinghui Guan; Cecile Chalouni; James Ziai; Yasin Şenbabaoğlu; Stephen Santoro; Daniel Sheinson; Jeffrey Hung; Jennifer M Giltnane; Andrew A Pierce; Kathryn Mesh; Steve Lianoglou; Johannes Riegler; Richard A D Carano; Pontus Eriksson; Mattias Höglund; Loan Somarriba; Daniel L Halligan; Michiel S van der Heijden; Yohann Loriot; Jonathan E Rosenberg; Lawrence Fong; Ira Mellman; Daniel S Chen; Marjorie Green; Christina Derleth; Gregg D Fine; Priti S Hegde; Richard Bourgon; Thomas Powles Journal: Nature Date: 2018-02-14 Impact factor: 49.962