Function-based classification of hazardous biological sequences: Demonstration of a new paradigm for biohazard assessments.

Bioengineering applies analytical and engineering principles to identify functional biological building blocks for biotechnology applications. While these building blocks are leveraged to improve the human condition, the lack of simplistic, machine-readable definition of biohazards at the function level is creating a gap for biosafety practices. More specifically, traditional safety practices focus on the biohazards of known pathogens at the organism-level and may not accurately consider novel biodesigns with engineered functionalities at the genetic component-level. This gap is motivating the need for a paradigm shift from organism-centric procedures to function-centric biohazard identification and classification practices. To address this challenge, we present a novel methodology for classifying biohazards at the individual sequence level, which we then compiled to distinguish the biohazardous property of pathogenicity at the whole genome level. Our methodology is rooted in compilation of hazardous functions, defined as a set of sequences and associated metadata that describe coarse-level functions associated with pathogens (e.g., adherence, immune subversion). We demonstrate that the resulting database can be used to develop hazardous "fingerprints" based on the functional metadata categories. We verified that these hazardous functions are found at higher levels in pathogens compared to non-pathogens, and hierarchical clustering of the fingerprints can distinguish between these two groups. The methodology presented here defines the hazardous functions associated with bioengineering functional building blocks at the sequence level, which provide a foundational framework for classifying biological hazards at the organism level, thus leading to the improvement and standardization of current biosecurity and biosafety practices.