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Hybrid De Novo Genome Assembly for the Generation of Complete Genomes of Urinary Bacteria using Short- and Long-read Sequencing Technologies
Published on: August 20, 2021
v MUS-dBG : A Novel De Bruijn Graph Model for De Novo Genome Assembly Using Variable-Length Minimum Unique Substrings
Andrews Frimpong Adu1, Elliot Sarpong Menkah2, Peter Amoako-Yirenkyi3
1Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi Ghana.
Research Square
|May 7, 2026
Summary
This study introduces a novel genome assembly method using variable-length Minimum Unique Substrings (MUS) instead of fixed k-mers in de Bruijn graphs (DBGs). This approach effectively handles genomic repeats and improves assembly contiguity and accuracy.
Area of Science:
- Genomics
- Bioinformatics
- Computational Biology
Background:
- De novo genome assembly commonly uses de Bruijn graphs (DBGs) with fixed k-mers.
- Fixed k-mer approaches face a trade-off between collapsing repeats (small k) and fragmentation (large k).
- Existing multi-k and variable-order methods have limitations in topology or parameter selection.
Purpose of the Study:
- To introduce a novel de Bruijn graph construction using Minimum Unique Substrings (MUSs).
- To develop a variable-length MUS de Bruijn graph (vMUS-dBG) that is repeat-aware and avoids global k-mer selection.
- To evaluate the performance of the vMUS-dBG approach for genome assembly.
Main Methods:
- Constructed a variable-length de Bruijn graph using Minimum Unique Substrings (MUSs) as nodes.
- Defined graph edges based on read-supported transitions between MUS occurrences.
- Incorporated instance-level metadata on edges for positional weights and support counts.
- Developed a prototype implementation for genome assembly using the vMUS-dBG.
Main Results:
- The vMUS-dBG approach eliminates the need for global k-mer selection.
- The graph construction is concrete and repeat-aware, differing from abstract DBG models.
- Experiments on E. coli K12 HiFi data showed comparable contiguity and accuracy to fixed-k methods.
- The MUS-based approach offers a principled, biologically grounded alternative.
Conclusions:
- Variable-length MUS de Bruijn graph construction is a viable alternative to fixed-k DBG assembly.
- This method provides a robust way to handle repeats in genome assembly.
- The vMUS-dBG framework offers a promising direction for future genome assembly research.
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