ISM

ISM identifies compact informative nucleotide sites (Informative Subtype Markers, ISMs) in SARS-CoV-2 genomes to enable genetic subtyping and tracking of spatiotemporal viral diversity.

Key Features:

• Entropy and frequency analysis: Employs an entropy measure followed by frequency analysis to identify Informative Subtype Markers representing the most variable nucleotide sites across viral genomes.
• ISM compression: Uses compression to detect covarying distant nucleotide variants, including non-coding and ORF1ab sites correlated with mutations such as D614G in the spike protein.
• Spatiotemporal visualization: Enables spatiotemporal visualization of ISM-defined subtypes using sequence data from the GISAID database.
• Complementary to phylogenetics: Provides a mutational-signature perspective that complements phylogenetic tree-based analyses of SARS-CoV-2 evolution.
• Dynamic pipeline: Dynamically generates and updates ISMs as new sequences are added.

Scientific Applications:

• Geographic and temporal monitoring: Monitor geographic distribution and temporal dynamics of SARS-CoV-2 subtypes.
• Regional subtype tracking: Define viral subtypes to track regional distributions and connections across continents.
• Mutation surveillance: Track the spread and prevalence of spike protein mutations such as D614G.
• Detection of local emergence: Detect emergence of distinct local subtypes, including examples in the United States linked to introductions from Asia.

Methodology:

Applies an entropy measure followed by frequency analysis to identify ISMs; applies compression to identify covarying distant nucleotide variants (including non-coding and ORF1ab sites correlated with D614G); uses sequence data from GISAID for spatiotemporal visualization; dynamically generates ISMs for newly added sequences.