Аннотация:In biological knowledge, a central task over centuries has been determining how do organisms ‘appear’ from the structural elements they are composed of. Reformulated, this question is about the functional organization of organisms: what are they composed of, and what the roles of the different elements are in this organization. Traditionally, this question has been addressed through top-down reductionistic approaches addressing individual elements (‘molecular pathways’). However, whereas such approaches provide a rich insight about lower-level elements and their interactions, they do not offer clues about how the higher level of organization (‘the organism’) emerges from such interactions: the possible number of work hypotheses is extremely large. To overcome this difficulty, we present an oppositely directed bottom-up approach based on inductive reasoning. In this methodology: 1) realizations of the ‘molecular pathway’ of interest in different contexts are compared, 2) following a strategy similar to that presented by Georg Pólya in his volumes of Mathematics and plausible reasoning (Pólya, 1954; 1968), the archetype (the “general case”) of the ‘molecular pathway’ of interest is conceived. By analyzing the archetype, functional roles of the ‘molecular pathway’ of interest are further inferred back in the specific contexts. As a result of this back-and-forth approach, that we denominate comparative functional architectonics, a reduced set of plausible and experimentally testable hypotheses is obtained about relevant functional ties linking organism-level traits (‘the phenotype’) with corresponding lower-level elements. We present the rules to apply the proposed methodology, together with examples of returned results taken from our previous studies following the comparative functional architectonic approach (Pérez Koldenkova and Hatsugai, 2017; Pérez Koldenkova and Hatsugai, 2018; Panina et al., 2020). This work is primarily intended for the community of ‘pathway biologists’: biologists whose research interests are related to the physiological relevance of particular ‘molecular pathways’, either in vitro or in vivo.