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Research Article

Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data

  • Alexander Mitsos,

    Affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Ioannis N. Melas,

    Affiliation: Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece

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  • Paraskeuas Siminelakis,

    Affiliation: Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece

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  • Aikaterini D. Chairakaki,

    Affiliation: Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece

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  • Julio Saez-Rodriguez,

    Affiliations: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Leonidas G. Alexopoulos mail

    leo@mail.ntua.gr

    Affiliation: Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece

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About the Authors

Alexander Mitsos
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
Ioannis N. Melas, Paraskeuas Siminelakis, Aikaterini D. Chairakaki, Leonidas G. Alexopoulos
Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece
Julio Saez-Rodriguez
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America
Julio Saez-Rodriguez
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

Corresponding Author

Email: leo@mail.ntua.gr

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: LGA. Performed the experiments: INM ADC LGA. Analyzed the data: INM PS ADC LGA. Contributed reagents/materials/analysis tools: AM JSR LGA. Wrote the paper: AM LGA. Conceived and formulated the integer linear program for the more efficient presentation of the Boolean model: AM. Implemented the formulation and linked to commercial solvers: AM. Provided access to commercial solvers (license-based): AM. Secondary inventor of the methodology for drug effects via drug-induced pathway alterations: AM. Wrote parts of the manuscript (mostly the computational part): AM. Run the computational case studies under the supervision of Alexopoulos and Mitsos: INM PS. Prepared the figures of the manuscript under the supervision of Alexopoulos: INM PS. Provided data/tools of previous approach for optimization of Boolean networks with genetic algorithm (GA): JSR. Assisted in the reformulation of the Boolean model and in the comparison with the GA approach: JSR. Edited the manuscript: JSR. Initiated and led the project and collaborations: LGA. Conceived the idea of using more sophisticated computational methods for fitting of experimental data after his initial discussion with AM: LGA. Provided the facilities and materials for the experiments: LGA. Main inventor of the methodology for finding drug effects via drug-induced pathway alteration: LGA. Wrote most of the paper: LGA.