Merkle, D. | bioRxiv Science

bioRxiv2025

Computational Approaches in Chemical Space Exploration for Carbon Fixation Pathways

Chemical space exploration is an important part of chemistry and biology, enabling the discovery and optimization of metabolic pathways, advancing synthetic metabolic functions, and understanding biochemical network evolution. We use a graph-based computational approach implemented in the cheminformatics software MOD, integrated with Integer Linear Programming (ILP) optimization, to systematically search chemical spaces. This approach allows for flexible and targeted queries, including identification of autocatalytic cycles, thermodynamic considerations, and discovery of novel enzymatic cascades. Specifically, we explore the chemical space of natural and artificial carbon fixation pathways defined from relevant enzyme reactions. By applying different optimization criteria, we identify new varieties and recombinations of natural autocatalytic pathways, and compare the properties of the pathways. This work highlights the versatility of graph-based cheminformatics for the purpose of chemical space exploration and artificial pathway design. Potential applications of this framework extend to carbon capture technologies, improved agricultural yields, and value-added chemical production, advancing efforts to address global sustainability challenges.

systems biology↗

bioRxiv2017

Time-Consistent Reconciliation Maps and ForbiddenTime Travel

BackgroundIn the absence of horizontal gene transfer it is possible to reconstruct the history of gene families from empirically determined orthology relations, which are equivalent to event-labeled gene trees. Knowledge of the event labels considerably simplifies the problem of reconciling a gene tree T with a species trees S, relative to the reconciliation problem without prior knowledge of the event types. It is well-known that optimal reconciliations in the unlabeled case may violate time-consistency and thus are not biologically feasible. Here we investigate the mathematical structure of the event labeled reconciliation problem with horizontal transfer.\n\nResultsWe investigate the issue of time-consistency for the event-labeled version of the reconciliation problem, provide a convenient axiomatic framework, and derive a complete characterization of time-consistent reconciliations. This characterization depends on certain weak conditions on the event-labeled gene trees that reflect conditions under which evolutionary events are observable at least in principle. We give an [O](|V(T)|log(|V(S)|))-time algorithm to decide whether a time-consistent reconciliation map exists. It does not require the construction of explicit timing maps, but relies entirely on the comparably easy task of checking whether a small auxiliary graph is acyclic. The algorithms are implemented in C++ using the boost graph library and are freely available at https://github.com/Nojgaard/tc-recon.\n\nSignificanceThe combinatorial characterization of time consistency and thus biologically feasible reconciliation is an important step towards the inference of gene family histories with horizontal transfer from orthology data, i.e., without presupposed gene and species trees. The fast algorithm to decide time consistency is useful in a broader context because it constitutes an attractive component for all tools that address tree reconciliation problems.

evolutionary biology↗