OligoDistiller: A Platform Agnostic Software Tool for MS and MS 2 Data Analysis of Complex Oligonucleotides and Their Impurities
Year: 2024
Type: article
Abstract: Oligonucleotides are currently one of the most rapidly advancing classes of therapeutic modalities. Understanding critical quality attributes, such as the impurity profile, stability, potential metabolites, and sequence conformity, is the key to their ultimate success. To obtain the information presented above, liquid chromatography–mass spectrometry (LC–MS) is often employed. However, data interpretation can be challenging due to multiple charge states, unknown species, chemical noises, and overlapping isotope envelopes (OIEs) of distinct but unresolved species. To address these challenges, we have developed an MS-platform agnostic, multifunctional R package and a web-tool for automated and interactive MS and MS 2 data analysis, OligoDistiller . From the MS spectrum of a complex mixture of two synthetic strands, our tool OligoDistiller annotated and quantified 45 oligonucleotide-related features including 13 unknown impurities and 6 OIEs, which all together explained 90.8% of the detected peaks. Also, major product ions were assigned from the MS 2 spectrum of a 47-mer DNA strand, covering 80.3% of the oligonucleotide sequence. We provide not only diverse isotope quality metrics for each annotated feature but also an interactive data review module allowing for direct inspection of the part of raw spectrum linked to a selected feature. This tool OligoDistiller is freely available at https://github.com/daniellyz/OligoDistiller .
Source: Analytical Chemistry
Authors: Youzhong Liu, Jennifer L. Lippens, Piotr Prostko, Ronald de Vries, Dirk Valkenborg, Thomas De Vijlder
Institution: Janssen (Belgium)
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Award: G8692724452
OpenAlex ID: W4405872818