article published yes Silke Asche author Carla Bautista author Celia Blanco author David Boulesteix author Alexandre Champagne-Ruel author Cole Mathis author Omer Markovitch author Zhen Peng author Avinash Vicholous Dass author Alyssa Adams author Eloi Camprubi author Enrico Sandro Colizzi author Stephanie Colón-Santos author Hannah Dromiack author Valentina Erastova author Amanda Garcia author Ghjuvan Grimaud author Aaron Halpern author Stuart A. Harrison author Seán F. Jordan author Tony Z. Jia author Amit Kahana author Artemy Kolchinsky author Odin Moron-Garcia author Ryo Mizuuchi author Jingbo Nan author Yuliia Orlova author Ben K.D. Pearce author Klaus Paschek author Martina Preiner author Silvana Pinna author Eduardo Rodríguez-Román author Loraine Schwander author Siddhant Sharma author 36996868-4916-11f1-8c9d-c0c901467b61 Harrison B. Smith author Andrey Vieira author Joana C. Xavier author The origin(s) of life (OoL), which has puzzled scientists for centuries, remains a major scientific challenge in the 21st century. Understanding the processes relevant to the OoL demands theoretical frameworks that can connect processes across scales, from microscopic dynamics to emergent levels of organization. While experimental studies generate a wealth of data, theoretical and computational approaches provide the structure necessary to interpret and generalize these findings. In Part 1, we examined the most widely used experimental techniques in the field. Here, we focus on the mathematical, physical, and computational techniques used to model phenomena relevant to life’s origin(s). We discuss methods ranging from quantum chemistry and molecular dynamics to chemical reaction networks, autocatalysis, and evolutionary modeling, as well as information-theoretic and phylogenetic approaches that link chemical and biological organization. We further highlight emerging trends such as synthetic biology, omics-based methods, and laboratory automation as novel points of contact for theory-experiment integration. Ultimately, we aim to provide an educational tool that can facilitate more post-disciplinary collaborations in OoL research by helping scientists understand what they can do about the problem of life’s origins, rather than telling them how to think about it. https://research-explorer.ista.ac.at/download/21753/21804/2026_CellReports_OoLEN.pdf application/pdfno Elsevier2026 eng 2666-386410.1016/j.xcrp.2026.103211 74 Asche, Silke, Carla Bautista, Celia Blanco, David Boulesteix, Alexandre Champagne-Ruel, Cole Mathis, Omer Markovitch, et al. “What It Takes to Solve the Origins of Life: An Integrated Review. Part 2: Theoretical Methods and Emerging Trends.” <i>Cell Reports Physical Science</i>. Elsevier, 2026. <a href="https://doi.org/10.1016/j.xcrp.2026.103211">https://doi.org/10.1016/j.xcrp.2026.103211</a>. Asche, Silke, et al. “What It Takes to Solve the Origins of Life: An Integrated Review. Part 2: Theoretical Methods and Emerging Trends.” <i>Cell Reports Physical Science</i>, vol. 7, no. 4, 103211, Elsevier, 2026, doi:<a href="https://doi.org/10.1016/j.xcrp.2026.103211">10.1016/j.xcrp.2026.103211</a>. S. Asche <i>et al.</i>, “What it takes to solve the origins of life: An integrated review. Part 2: Theoretical methods and emerging trends,” <i>Cell Reports Physical Science</i>, vol. 7, no. 4. Elsevier, 2026. Asche S, Bautista C, Blanco C, et al. What it takes to solve the origins of life: An integrated review. Part 2: Theoretical methods and emerging trends. <i>Cell Reports Physical Science</i>. 2026;7(4). doi:<a href="https://doi.org/10.1016/j.xcrp.2026.103211">10.1016/j.xcrp.2026.103211</a> S. Asche, C. Bautista, C. Blanco, D. Boulesteix, A. Champagne-Ruel, C. Mathis, O. Markovitch, Z. Peng, A.V. Dass, A. Adams, E. Camprubi, E.S. Colizzi, S. Colón-Santos, H. Dromiack, V. Erastova, A. Garcia, G. Grimaud, A. Halpern, S.A. Harrison, S.F. Jordan, T.Z. Jia, A. Kahana, A. Kolchinsky, O. Moron-Garcia, R. Mizuuchi, J. Nan, Y. Orlova, B.K.D. Pearce, K. Paschek, M. Preiner, S. Pinna, E. Rodríguez-Román, L. Schwander, S. Sharma, H.B. Smith, A. Vieira, J.C. Xavier, Cell Reports Physical Science 7 (2026). Asche S, Bautista C, Blanco C, Boulesteix D, Champagne-Ruel A, Mathis C, Markovitch O, Peng Z, Dass AV, Adams A, Camprubi E, Colizzi ES, Colón-Santos S, Dromiack H, Erastova V, Garcia A, Grimaud G, Halpern A, Harrison SA, Jordan SF, Jia TZ, Kahana A, Kolchinsky A, Moron-Garcia O, Mizuuchi R, Nan J, Orlova Y, Pearce BKD, Paschek K, Preiner M, Pinna S, Rodríguez-Román E, Schwander L, Sharma S, Smith HB, Vieira A, Xavier JC. 2026. What it takes to solve the origins of life: An integrated review. Part 2: Theoretical methods and emerging trends. Cell Reports Physical Science. 7(4), 103211. Asche, S., Bautista, C., Blanco, C., Boulesteix, D., Champagne-Ruel, A., Mathis, C., … Xavier, J. C. (2026). What it takes to solve the origins of life: An integrated review. Part 2: Theoretical methods and emerging trends. <i>Cell Reports Physical Science</i>. Elsevier. <a href="https://doi.org/10.1016/j.xcrp.2026.103211">https://doi.org/10.1016/j.xcrp.2026.103211</a> 217532026-04-19T22:07:50Z2026-05-07T12:13:07Z