K-FluDB: A Novel K-Mer Based Database for Enhanced Genomic Surveillance of Influenza A Viruses

K-FluDB is a compressed database composed of distinct sub-sequences specific to 50 influenza A subtypes. It includes subtype-specific sequences for all 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes. The original influenza sequences were obtained from the NCBI database on May 8, 2022, comprising a total of 895,900 Influenza A sequences.

To generate this database, sequences were first subsampled based on genomic segment and variant group, resulting in 81,262 sequences. These sequences served as input for the PanGen-InfluenzaA tool (GitHub), which constructs pangenomes by identifying both subtype-specific sequences and sequences shared across multiple subtypes.

Repository Contents

This repository contains a ZIP archive with three folders, each corresponding to pangenome datasets designed for reads of 75, 150, and 300 nucleotides in length. Each folder includes the following files:

• Dispensable data files (1_dispensable.fasta to 8_dispensable.fasta):
  These files contain the dispensable genomic fragments for each of the eight segments of the Influenza A virus.

• Subtype-specific data files (1_specific.fasta to 8_specific.fasta):
  These files contain the subtype-specific genomic fragments for each segment. The recommended files for mapping against genomic reads are 4_specific.fasta and 6_specific.fasta, corresponding to segments 4 and 6, which are the targets commonly used for Influenza A subtyping.

Within each core directory (75, 150, and 300), three distinct subdirectories—specific, pangenome, and dispensable—contain the pangenome files stratified by subtype. Specifically, the files located in the specific subdirectories for segments 4 and 6 are the recommended datasets for use in subtype identification during subsequent genomic analysis.

Compression Efficiency and Classification Accuracy

K-FluDB achieves a relative compression index of 96.54% when using the complete pangenome and 99.64% when considering only subtype-specific sequences. The average precision for correctly classifying Hx and Nx subtypes using the subtype-specific sequences is 99.2% and 99.71%, respectively.

This database provides a highly efficient and accurate resource for influenza A subtype classification while significantly reducing the storage and computational requirements associated with full-genome analyses.

This work has been supported by the Universidad Nacional Autónoma de México grant number [PAPIIT-DGAPA-IN230523] granted to Blanca Taboada and Secretaría de Educación, Ciencia, Tecnología e Innovación de la Ciudad de México with grant number [SECTEI/138/2024] granted to Selene Zárate.
The first author gratefully acknowledges the scholarship provided by CONAHCYT. We also extend our sincere appreciation to the National Autonomous University of Mexico (UNAM) for grant-ing access to the MIZTLI supercomputer, supported by the Gen-eral Directorate of Computing and Information and Communica-tion Technologies (DGTIC) through project LANCAD-UNAM-DGTIC-350. Lastly, we wish to thank Jerome Verleyen, Juan Manuel Hurtado, and Roberto Bahena from UNAM’s Instituto de Biotecnología for their indispensable assistance with computation-al support.