INTRODUCTION • The concept of “cell type” is loose scientifically • The Human Cell Atlas (HCA) needs a firm conceptual basis to ensure consistency • We dissect the concept of “cell type”, providing solid foundations for organizing our knowledge about cells, both in core Human Cell Atas database and in scientific discourse atomic cell types and species-centric divisions form a solid basis for organizing knowledge RESULTS Sensu stricto types, archetypes, infratypes and technotypes: a framework for cell classiﬁcation Tiago Lubiana (presenting) and Helder Nakaya Computational Systems Biology Laboratory - INOVA USP , University of São Paulo, Brazil Scan for extra methods and references email: tiago.lubiana.alves@usp.br github: @lubianat DISCUSSION ●Experiments generate knowledge at the technotype level ●Scientiﬁc articles work at the infratype level (ex: a single mouse strain) ●Reviews usually talk about the species level (ex: Arendt’s evolutionary types) ●Most general biology textbooks work at the archetype level ●Inference from a lower level to a higher one is not logically guaranteed ●HCA should be aware of the species-centric level of cell types in its products, to avoid false conclusions and inconsistency in every case to avoid false conclusions ATOMIC CELL TYPES AND QUALIFIERS ●Archetypes: cell type ideas applicable across multiple species ●Sensu stricto cell types: cell type ideas restricted to a single species ●Infratypes: cell type ideas restricted to a sub-specific population ●Technotypes: cell type ideas describing the objects of cell-population-centric experiments ●cell class: any concept referring to a set of real-world biological cells ●atomic cell type: the indivisible idea for a cell class given its factorization in qualifying slots in a particular context. ●qualifying slots: fields capturing continuous and discrete and sources of diversity SPECIES-CENTRIC DIVISIONS OF “CELL TYPE” SPECIES-CENTRIC DIVISIONS ●Any idea referring to real-world cell classes can be split in an atomic cell type plus one or more qualiﬁers ●HCA needs to clarify its desired qualifying slots for effective knowledge management ●The Cell Ontology needs to provide IDs for all atomic cell types needed by HCA resources ●To avoid competing annotations, resources should cover species as a slot, and only use Cell Ontologies` archetypes ●By parsing out transient and fortuitous qualiﬁers into slots, atomic cell types may correspond to a set of natural stable property clusters (SPCs) ●Technotypes are atomic cell types capturing all possible qualiﬁers in the context of an experiment. They would be relevant for granular representation of experiments in knowledge graphs ATOMIC CELL TYPES HOW TO CATALOG ALL HUMAN CELL TYPES 1. Pick a set of cell classes of theoretical interest at the species level 2. Select all relevant qualifying slots 3. Factorize cell classes in qualifiers and atomic cell types 4. Select or mint IDs for each term 5. Iterate until no new atomic types are seen 6. To get all relevant classes, set valid combinations and computationally infer them Ex: “bone types” x “osteocyte”x “sex” … → male femur osteocyte, female tibia osteocyte This work is supported by FAPESP GRANT #19/26284-1