Annotation of Functions of Sequences of Concern and Its Relevance to the New Biosecurity Regulatory Framework in the United States.

Introduction: Recent regulations from United States Government agencies reshape the screening of synthetic nucleic acids. These take a step away from categorizing hazard on the basis of "bad" taxa and invoke the function of the sequence in pathogenesis or intoxication. Ascertaining functions related to pathogenesis and distinguishing these from other molecular abilities that are unproblematic is not simple.

Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern.

Regulation of research on microbes that cause disease in humans has historically been focused on taxonomic lists of 'bad bugs'. However, given our increased knowledge of these pathogens through inexpensive genome sequencing, 5 decades of research in microbial pathogenesis, and the burgeoning capacity of synthetic biologists, the limitations of this approach are apparent. With heightened scientific and public attention focused on biosafety and biosecurity, and an ongoing review by US authorities of dual-use research oversight, this article proposes the incorporation of sequences of concern (SoCs) into the biorisk management regime governing genetic engineering of pathogens.

SeqScreen: accurate and sensitive functional screening of pathogenic sequences via ensemble learning.

The COVID-19 pandemic has emphasized the importance of accurate detection of known and emerging pathogens. However, robust characterization of pathogenic sequences remains an open challenge. To address this need we developed SeqScreen, which accurately characterizes short nucleotide sequences using taxonomic and functional labels and a customized set of curated Functions of Sequences of Concern (FunSoCs) specific to microbial pathogenesis.

Categorizing Sequences of Concern by Function To Better Assess Mechanisms of Microbial Pathogenesis.

To identify sequences with a role in microbial pathogenesis, we assessed the adequacy of their annotation by existing controlled vocabularies and sequence databases. Our goal was to regularize descriptions of microbial pathogenesis for improved integration with bioinformatic applications. Here, we review the challenges of annotating sequences for pathogenic activity.

Simulating transmission of ESKAPE pathogens plus C. difficile in relevant clinical scenarios.

Background: The prevalence of healthcare-acquired infections (HAI) and rising levels of antimicrobial resistance places significant economic and public health burdens on modern healthcare systems. A group of highly drug resistant pathogens known as the ESKAPE pathogens, along with C. difficile, are the leading causes of HAIs.

A Rho-like small GTPase of Entamoeba histolytica contains an unusual amino acid residue in a conserved GDP-stabilization region and is not a substrate for C3 exoenzyme.

The Entamoeba histolytica small GTP-binding protein EhRho1 has an unusual amino acid residue at a conserved site found in all known Ras superfamily proteins. EhRho1 has an isoleucine at position 45, which corresponds to position 28 of human Ras and Rac and position 30 of human Rho and Cdc42. All other known small GTPases have an aromatic residue (typically phenylalanine) at this position, and mutation to a leucine renders other Ras proteins constitutively active by reason of diminished affinity for GDP.