Model Integration in Computational Biology: The Role of Reproducibility, Credibility and Utility

Abstract

During the COVID-19 pandemic, mathematical modeling of disease transmission has become a cornerstone of key state decisions. To advance the state-of-the-art host viral modeling to handle future pandemics, many scientists working on related issues assembled to discuss the topics. These discussions exposed the reproducibility crisis that leads to inability to reuse and integrate models. This document summarizes these discussions, presents difficulties, and mentions existing efforts towards future solutions that will allow future model utility and integration. We argue that without addressing these challenges, scientists will have diminished ability to build, disseminate, and implement high-impact multi-scale modeling that is needed to understand the health crises we face.

Artificial Intelligence and Anticancer Drug Development—Keep a Cool Head

“…It, thus, appears necessary for health authorities to thoroughly revise the rules for setting up clinical trials, incorporating AI and in silico methodology [ 26 ]. These rules will have to include the notion of result reproducibility if they are to be accepted by the medical and scientific community [ 27 ].…”

Drug Development Digital Twins for Drug Discovery, Testing and Repurposing: A Schema for Requirements and Development

“…• There are two primary barriers that limit existing computational models and modules from being utilized as DDDTs: 1) they are not typically inter-compatible without significant software engineering efforts, rendering systems-level simulations difficult or low-resolution; and 2) the focus at present is typically on separating "the signal from the noise," and in doing so, washing away complexity that leads to biological heterogeneity. Both of these challenges are readily addressable: • Towards the first challenge, there has been extensive work on developing mechanism-based simulation models on various pathophysiological processes, and the critical issues regarding model sharing, credibility assessment and reuse have been recently cataloged in (Saccenti, 2021;Karr et al, 2022). The importance of model repositories and consortia development have been discussed in other papers concerning medical digital twins (Björnsson et al, 2020;Laubenbacher et al, 2021;Masison et al, 2021) • Addressing the second challenge is necessary for the "Discovery" portion of the DDDT.…”

“…Towards the first challenge, there has been extensive work on developing mechanism-based simulation models on various pathophysiological processes, and the critical issues regarding model sharing, credibility assessment and reuse have been recently cataloged in ( Saccenti, 2021 ; Karr et al, 2022 ). The importance of model repositories and consortia development have been discussed in other papers concerning medical digital twins ( Björnsson et al, 2020 ; Laubenbacher et al, 2021 ; Masison et al, 2021 )…”

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“…Studying epithelial dynamics at relevant biological scales necessitates the construction of reproducible, reusable computational models 13 . Most software implementations of published VMs are either not publicly available, or are single-use implementations with limited to no support for usage and extension by others.…”