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Background  Application oriented ontologies are important for reliably communicating and managing data in databases. Unfortunately, they often differ in the definitions they use and thus do not live up to their potential. This problem can be reduced when using a standardized and ontologically consistent template for the top-level categories from a top-level formal foundational ontology. This would support ontological consistency within application oriented ontologies and compatibility between them. The Basic Formal Ontology (BFO) is such a foundational ontology for the biomedical domain that has been developed following the single inheritance policy. It provides the top-level template within the Open Biological and Biomedical Ontologies Foundry. If it wants to live up to its expected role, its three top-level categories of material entity (i.e., ‘object’, ‘ fiat  object part’, ‘object aggregate’) must be exhaustive, i.e. every concrete material entity must instantiate exactly one of them.    Methodology/Principal Findings  By systematically evaluating all possible basic configurations of material building blocks we show that BFO's top-level categories of material entity are not exhaustive. We provide examples from biology and everyday life that demonstrate the necessity for two additional categories: ‘ fiat  object part aggregate’ and ‘object with  fiat  object part aggregate’. By distinguishing topological coherence, topological adherence, and metric proximity we furthermore provide a differentiation of clusters and groups as two distinct subcategories for each of the three categories of material entity aggregates, resulting in six additional subcategories of material entity.    Conclusions/Significance  We suggest extending BFO to incorporate two additional categories of material entity as well as two subcategories for each of the three categories of material entity aggregates. With these additions, BFO would exhaustively cover all top-level types of material entity that application oriented ontologies may use as templates. Our result, however, depends on the premise that all material entities are organized according to a constitutive granularity.

Top-Level Categories of Constitutively Organized Material Entities - Suggestions for a Formal Top-Level Ontology