From data to QSP models: a pipeline for using Boolean networks for hypothesis inference and dynamic model building

Teaching computational systems biology with an eye on quantitative systems pharmacology at the undergraduate level: Why do it, who would take it, and what should we teach?

“…At the time, my experimental collaborator, an "old fashioned, hardcore, card-carrying" biologist, described to me his first microarray experiments as follows "it felt like I had spent my entire life looking at a tree in my backyard while sitting on my porch and suddenly I climbed the roof of my house and realized I could see the forest." This is, I believe, a very nice description of SB, especially as we merge SB with pharmacology and physiology into what is now referred to as quantitative systems pharmacology (Vodovotz et al, 2013;Androulakis, 2015;Rao et al, 2016a;Scheff et al, 2016;Putnins et al, 2022). Looking beyond the tree closest to us, not only at all the other trees but also at all other living and nonliving things one can find in a forest, and realizing how they depend on each other, changes our perspective.…”

“…1) QSP methodology toolboxes (Cheng et al, 2017;Ribba et al, 2017;Ermakov et al, 2019;Kirouac et al, 2019;Chae, 2020;Derbalah et al, 2020;Hosseini et al, 2020;Gong et al, 2021) 2) QSP applications (Rieger and Musante, 2016;Stein and Looby, 2018) 3) QSP applications (Bai et al, 2014;Gadkar et al, 2014;Gadkar et al, 2015;Lu et al, 2015;Allen et al, 2016;Rieger and Musante, 2016) 4) Translational aspects of mathematical models (Foteinou et al, 2009;Foteinou et al, 2011) 5) Boolean (Putnins and Androulakis, 2019;Putnins and Androulakis, 2021;Putnins et al, 2022) and agent-based (Dong et al, 2010;Nguyen et al, 2013) modeling.…”

“…Boolean ( Putnins and Androulakis, 2019 ; Putnins and Androulakis, 2021 ; Putnins et al, 2022 ) and agent-based ( Dong et al, 2010 ; Nguyen et al, 2013 ) modeling.…”

“…A computational model focused on extensive data analysis using (mostly) black box approaches to replicate the observed dynamics. Indeed, they can be based on theoretical or mathematical foundations, but the emphasis is on computational methodologies ( Putnins and Androulakis, 2019 ; Putnins et al, 2022 ). A neural network is a typical example of a computational model ( Yazdani et al, 2020 ; Przedborski et al, 2021 ).…”

Editor’s note on the themed issue: integration of machine learning and quantitative systems pharmacology

“…• Mager and colleagues first introduced Boolean network models to pharmacometrics just a few years ago by demonstrating how this new methodology can be used to build and simplify QSP models prior to development of more formal ordinary differential equation-based models [18][19][20]. Putnins et al [21] further develop this methodology by implementing a pipeline approach to simplify and standardize network model development.…”