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bioRxiv · 10.1101/2022.06.27.496265

Frugal alignment-free identification of FLT3-internal tandem duplications with FiLT3r

Boudry, A.·Darmon, S.·Duployez, N.·Figeac, M.·Geffroy, S.·Bucci, M.·Celli-Lebras, K.·Duchmann, M.·Joudinaud, R.·Fenwarth, L.·Nibourel, O.·Goursaud, L.·Itzykson, R.·Dombret, H.·Hunault, M.·Preudhomme, C.·Salson, M.
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Abstract

BackgroundInternal tandem duplications in the FLT3 gene, termed FLT3-ITDs, are useful molecular markers in acute myeloid leukemia (AML) for patient risk stratification and follow-up. FLT3-ITDs are increasingly screened through high-throughput sequencing (HTS) raising the need for robust and efficient algorithms. We developed a new algorithm, which performs no alignment and uses little resources, to identify and quantify FLT3-ITDs in HTS data. ResultsOur algorithm (FiLT3r) focuses on the k-mers from reads covering FLT3 exons 14 and 15. We show that those k-mers bring enough information to accurately detect, determine the length and quantify FLT3-ITD duplications. We compare the performances of FiLT3r to state-of-the-art alternatives and to fragment analysis, the gold standard method, on a cohort of 185 AML patients sequenced with capture-based HTS. On this dataset FiLT3r is more precise (no false positive nor false negative) than the other software evaluated. We also assess the software on public RNA-Seq data, which confirms the previous results and shows that FiLT3r requires little resources compared to other software. ConclusionFiLT3r is a free software available at https://gitlab.univ-lille.fr/filt3r/filt3r. The repository also contains a Snakefile to reproduce our experiments. We show that FiLT3r detects FLT3-ITDs better than other software while using less memory and time.

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Boudry, A., Darmon, S., Duployez, N., Figeac, M., Geffroy, S., Bucci, M., Celli-Lebras, K., Duchmann, M., Joudinaud, R., Fenwarth, L., Nibourel, O., Goursaud, L., Itzykson, R., Dombret, H., Hunault, M., Preudhomme, C., Salson, M.. 2022-06-29. Frugal alignment-free identification of FLT3-internal tandem duplications with FiLT3r. https://doi.org/10.1101/2022.06.27.496265

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