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bioRxiv · 10.1101/2024.05.03.592314

LBFextract: unveiling transcription factor dynamics from liquid biopsy data

Lazzeri, I.·Spiegl, B.·Hasenleithner, S. O.·Speicher, M. R.·Kircher, M.
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Abstract

Structured abstractO_ST_ABSMotivationC_ST_ABSThe analysis of circulating cell-free DNA (cfDNA) holds immense promise as a non-invasive diagnostic tool across various human conditions. However, extracting biological insights from cfDNA fragments entails navigating complex and diverse bioinformatics methods, encompassing not only DNA sequence variation but also epigenetic characteristics like nucleosome footprints, fragment length, and methylation patterns. ResultsWe introduce LBFextract, a comprehensive package designed to streamline feature extraction from cfDNA data, with the aim of enhancing the reproducibility and comparability of liquid biopsy studies. LBFextract facilitates the integration of preprocessing and postprocessing steps through alignment fragment tags and a hook mechanism. It incorporates various methods, including coverage-based and fragment length-based approaches, alongside two novel feature extraction methods: an entropy-based method to infer TF activity from fragmentomics data and a technique to amplify signals from nucleosome dyads. Additionally, it implements a method to extract condition-specific differentially active TFs based on these features for biomarker discovery. We demonstrate the use of LBFextract for the subtype classification of advanced prostate cancer patients using coverage signals at transcription factor binding sites from cfDNA. We show that LBFextract can generate robust and interpretable features that can discriminate between different clinical groups. LBFextract is a versatile and user-friendly package that can facilitate the analysis and interpretation of liquid biopsy data. Data and Code Availability and ImplementationLBFextract is freely accessible at https://github.com/Isy89/LBF. It is implemented in Python and compatible with Linux and Mac operating systems. Code and data to reproduce these analyses have been uploaded to 10.5281/zenodo.10964406. ContactFor further information, contact isaac.lazzeri@medunigraz.at, samantha.hasenleithner@medunigraz.at, martin.kircher@bih-charite.de. Supplementary InformationFor additional details see Supplementary Information. For usage of the package, refer to https://lbf.readthedocs.io/.

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Lazzeri, I., Spiegl, B., Hasenleithner, S. O., Speicher, M. R., Kircher, M.. 2024-05-05. LBFextract: unveiling transcription factor dynamics from liquid biopsy data. https://doi.org/10.1101/2024.05.03.592314

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