LIN codes for Corynebacterium diphtheriae
cgMLST-based Life Identification Numbers for Genomic Taxonomy of C. diphtheriae strains
Quick Presentation of Corynebacterium diphtheriae LIN codes
The cgMLST-based Life Identification Numbers (LIN) codes (cgLIN codes, or LIN codes for short) constitute a novel genomic taxonomy system for bacterial strains within species. An implementation of LIN codes was specifically developed for strains of Corynebacterium diphtheriae and its closely related species C. belfantii and C. rouxii. This system provides a stable, hierarchical classification framework that captures phylogenetic diversity from species level down to near genetic identity levels, useful for epidemiological surveillance (see Palma, Hennart et al. for general information on LIN codes; and Delgado-Blas et al. for application to C. diphtheriae).
General Presentation
The LIN code system for Corynebacterium diphtheriae is built upon a core-genome Multi-Locus Sequence Typing (cgMLST) scheme comprising 1,305 conserved loci. This represents a significant advancement from the classical 7-loci MLST approach, enabling much higher-resolution strain typing and providing a stable nomenclature.
A LIN code is a multi-position integer-based code attributed to each genome based on its cgMLST profile. The C. diphtheriae LIN code system consists of 10 fixed, ordered bins that determine partitions of the [0%-100%] range of cgMLST profile similarity. Each bin is defined by lower (inclusive) and upper (exclusive) similarity thresholds, with leftmost bins capturing broad phylogenetic divisions and rightmost bins capturing fine-scale genetic relationships suitable for epidemiological surveillance and outbreak investigation.
Additional information on LIN code fundamental concepts, LIN code attribution process and LIN code implementation in external platforms can be found at the page of the first cgMLST LIN code implementation https://bigsdb.pasteur.fr/klebsiella/cgmlst-lincodes/, and in the publication Palma, Hennart et al..
Table 1. Taxonomic levels and associated thresholds of the LIN code strain taxonomy for C. diphtheriae
| bin | classification | No. allele mismatches | No. identical alleles | % allele similarity | Purpose |
|---|---|---|---|---|---|
| 1 | Species | [1305-1240[ | [0-65[ | [0.00-4.98[ | Phylogenetic level |
| 2 | Lineage | [1240-1035[ | [65-270[ | [4.98-20.69[ | Phylogenetic level |
| 3 | Sublineage (SL) | [1035-500[ | [270-805[ | [20.69-61.69[ | Phylogenetic level |
| 4 | Clonal Group (ClG) | [500-55[ | [805-1250[ | [61.69-95.78[ | Phylogenetic level |
| 5 | Genetic Cluster (GC) | [55-25[ | [1250-1280[ | [95.78-98.08[ | Phylogenetic level |
| 6 | - | [25-8[ | [1280-1297[ | [98.08-99.39[ | Epidemiological level |
| 7 | - | [8-4[ | [1297-1301[ | [99.39-99.69[ | Epidemiological level |
| 8 | - | [4-2[ | [1301-1303[ | [99.69-99.85[ | Epidemiological level |
| 9 | - | [2-1[ | [1303-1304[ | [99.85-99.92[ | Epidemiological level |
| 10 | - | [1-0[ | [1304-1305[ | [99.92-100.00[ | Epidemiological level |
Source database of the LIN codes
For obvious consistency purposes, there should be only one source database for the LIN code definitions. The source of LIN codes for C. diphtheriae species complex genomes is hosted at the BIGSdb-Pasteur strain taxonomy platform (https://bigsdb.pasteur.fr/diphtheria/).
A human-readable nomenclature of genetic clusters and sublineages: nicknames of LIN code prefixes
The LIN codes can be used as a nomenclatural system per se, but it is more convenient to use human-readable and easy to remember nicknames to designate important groups. In the C. diphtheriae species complex, all existing prefixes (an incomplete part of the LIN code starting at its leftmost bin, of size 1 to 9) corresponding to the first five levels of the LIN codes are automatically attributed aliases (or nicknames). This enables backward compatibility and easier communication between microbiologists and epidemiologists using LIN codes.
To maximize continuity with established nomenclatures, these nicknames were chosen based on previously existing nomenclatures. The first level (prefix of size 1) was nicknamed with the Linnaean species taxonomy (table 2).
Table 2. The correspondence between the first LIN code level and species taxonomy
| LIN Prefix | Species |
|---|---|
| 0_ | C. diphtheriae |
| 1_ | C. rouxii |
| 2_ | C. belfantii |
Levels 3, 4, and 5 of the LIN codes correspond to the deepest classification levels within species, called 'sublineage' (SL), 'clonal group' (ClG), and 'genetic cluster' (GC), respectively (Table 3). SL and ClG nicknames correspond (where possible) to the predominant 7-gene MLST sequence type within each taxonomic group, creating a dictionary between MLST identifiers and these two LIN code-based classification levels. In turn, GC nicknames were initially assigned by decreasing total genome counts in the database (as of 2025) and are now being incremented by one automatically. This level is particularly relevant for epidemiological investigations, as it provides resolution useful for outbreak detection and surveillance of transmission events.
Table 3. Examples of LIN code prefixes, nicknames and corresponding 7-gene MLST classification for major sublineages (SL) and genetic clusters (GC)
| LIN Prefix (3-level) | SL Nickname | LIN Prefix (4-level) | ClG Nickname | Majority STs | LIN Prefix (5-level) | GC Nickname |
|---|---|---|---|---|---|---|
| 0_0_0 | SL8 | 0_0_0_0 | ClG8 | ST8 | 0_0_0_0_0 | GC29 |
| 0_0_0 | SL8 | 0_0_0_0 | ClG8 | ST8 | 0_0_0_0_2 | GC37 |
| 0_0_0 | SL8 | 0_0_0_0 | ClG8 | ST8 | 0_0_0_0_5 | GC32 |
| 0_0_18 | SL384 | 0_0_18_0 | ClG384 | ST384 | 0_0_18_0_0 | GC3 |
| 0_0_21 | SL377 | 0_0_21_0 | ClG377 | ST377 | 0_0_21_0_4 | GC2 |
| 0_0_85 | SL574 | 0_0_85_1 | ClG574 | ST574 | 0_0_85_1_0 | GC1 |
| 0_0_30 | SL228 | 0_0_30_0 | ClG228 | ST228 | 0_0_30_0_0 | GC15 |
| 0_0_47 | SL416 | 0_0_47_0 | ClG416 | ST416 | 0_0_47_0_0 | GC12 |
Implementation and Database Access
BIGSdb-Pasteur Platform
The C. diphtheriae LIN code system is implemented and maintained within the BIGSdb-Pasteur platform. This platform serves as the authoritative source for:
🧬 cgMLST allele and profile definitions
🔗 LIN code definitions and assignments
🏷️ Nickname assignments
🌐 Standardized nomenclature platform for global comparative genomics
BIGSdb-Pasteur diphtheria database URL: https://bigsdb.pasteur.fr/diphtheria/
Advantages of Using the LIN code Nomenclature
The LIN code system for C. diphtheriae offers several critical advantages over traditional typing methods:
- Enhanced Phylogenetic Resolution
- The 1,305 loci (vs. 7 in traditional MLST) provide ~186× more genomic information. The high number of genetic markers provide meaningful phylogenetic context.
- They provide high genetic discrimination between isolates that may appear identical by traditional typing methods.
- Isolates from single patients or transmission chains have identical LIN codes or nearly so.
- Nomenclatural Stability and Backwards Compatibility
- LIN codes are stable by design, avoiding the group fusion issues of single-linkage clustering or other unstable classifications.
- Once assigned, LIN codes remain static regardless of new genome additions.
- Human-readable nicknames provide continuity with established MLST nomenclature.
- Shared nomenclature enables global communication, unlike local or private nomenclatures, and provides precise phylogenetic context, unlike arbitrary ST numbers.
- Flexible Cluster Analysis Using Multiple Levels
- The 10 hierarchical levels accommodate diverse biological questions or epidemiological investigations.
- LIN codes enable diverse analyses from broad population structure (species/lineages) to fine-scale transmission (0–8 allelic differences).
- Shared LIN prefixes indicate minimum and maximum similarity levels, providing genetic relatedness information embedded within the LIN codes.
Data Submission and Curation
For consistency and accuracy, there should ideally be only one source for C. diphtheriae LIN code definitions. Researchers are encouraged to submit genomic data to the BIGSdb-Pasteur platform for LIN code assignment and integration into the shared C. diphtheriae genomic taxonomy.
📋 Submission Guidelines: https://bigsdb.pasteur.fr/submission-procedure-for-data-curation/
Key References
Delgado-Blas JF, Rethoret-Pasty M, Brisse S. Life Identification Number (LIN) codes for the genomic taxonomy of Corynebacterium diphtheriae strains. Genome Medicine. 2025;18:5. https://doi.org/10.1186/s13073-025-01579-6
Palma F, Hennart M, Jolley KA, Crestani C, Wyres KL, Bridel S, Yeats CA, Brancotte B, Raffestin B, David S, Lam MMC, Izdebski R, Passet V, Rodrigues C, Rethoret-Pasty M, Combary A, Cottis S, Maiden MCJ, Aanensen DM, Holt KE, Criscuolo A, Brisse S. Life Identification Numbers: Life Identification Numbers: A strain nomenclature approach to aid epidemiological surveillance of bacterial pathogens. PLoS Biol. 2026 Jun 4;24(6):e3003781. https://doi.org/10.1371/journal.pbio.3003781
Guglielmini J, Hennart M, Badell E, Toubiana J, Criscuolo A, Brisse S. Genomic Epidemiology and Strain Taxonomy of Corynebacterium diphtheriae. J Clin Microbiol. 2021;59(12):e0158121. https://doi.org/10.1128/jcm.01581-21
Hennart M, Guglielmini J, Bridel S, Maiden MCJ, Jolley KA, Criscuolo A, Brisse S. A Dual Barcoding Approach to Bacterial Strain Nomenclature: Genomic Taxonomy of Klebsiella pneumoniae Strains. Mol Biol Evol. 2022;39(7):msac135. https://doi.org/10.1093/molbev/msac135