Disentangling the Complex Multiplexed DIA Spectra in De Novo Peptide Sequencing

Fuente: arXiv
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Autori principali: Ma, Zheng, Mao, Zeping, Zhang, Ruixue, Chen, Jiazhen, Xin, Lei, Shan, Baozhen, Ghodsi, Ali, Li, Ming
Natura: Preprint
Pubblicazione: 2024
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author Ma, Zheng
Mao, Zeping
Zhang, Ruixue
Chen, Jiazhen
Xin, Lei
Shan, Baozhen
Ghodsi, Ali
Li, Ming
author_facet Ma, Zheng
Mao, Zeping
Zhang, Ruixue
Chen, Jiazhen
Xin, Lei
Shan, Baozhen
Ghodsi, Ali
Li, Ming
contents Data-Independent Acquisition (DIA) was introduced to improve sensitivity to cover all peptides in a range rather than only sampling high-intensity peaks as in Data-Dependent Acquisition (DDA) mass spectrometry. However, it is not very clear how useful DIA data is for de novo peptide sequencing as the DIA data are marred with coeluted peptides, high noises, and varying data quality. We present a new deep learning method DIANovo, and address each of these difficulties, and improves the previous established systems by a large margin, via equipping the model with a deeper understanding of coeluted DIA spectra. This paper also provides criteria about when DIA data could be used for de novo peptide sequencing and when not to by providing a comparison between DDA and DIA, in both de novo and database search mode. We find that while DIA excels with narrow isolation windows on older-generation instruments, it loses its advantage with wider windows. However, with Orbitrap Astral, DIA consistently outperforms DDA due to narrow window mode enabled. We also provide a theoretical explanation of this phenomenon, emphasizing the critical role of the signal-to-noise profile in the successful application of de novo sequencing.
format Preprint
id arxiv_https___arxiv_org_abs_2411_15684
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Disentangling the Complex Multiplexed DIA Spectra in De Novo Peptide Sequencing
Ma, Zheng
Mao, Zeping
Zhang, Ruixue
Chen, Jiazhen
Xin, Lei
Shan, Baozhen
Ghodsi, Ali
Li, Ming
Biomolecules
Machine Learning
Data-Independent Acquisition (DIA) was introduced to improve sensitivity to cover all peptides in a range rather than only sampling high-intensity peaks as in Data-Dependent Acquisition (DDA) mass spectrometry. However, it is not very clear how useful DIA data is for de novo peptide sequencing as the DIA data are marred with coeluted peptides, high noises, and varying data quality. We present a new deep learning method DIANovo, and address each of these difficulties, and improves the previous established systems by a large margin, via equipping the model with a deeper understanding of coeluted DIA spectra. This paper also provides criteria about when DIA data could be used for de novo peptide sequencing and when not to by providing a comparison between DDA and DIA, in both de novo and database search mode. We find that while DIA excels with narrow isolation windows on older-generation instruments, it loses its advantage with wider windows. However, with Orbitrap Astral, DIA consistently outperforms DDA due to narrow window mode enabled. We also provide a theoretical explanation of this phenomenon, emphasizing the critical role of the signal-to-noise profile in the successful application of de novo sequencing.
title Disentangling the Complex Multiplexed DIA Spectra in De Novo Peptide Sequencing
topic Biomolecules
Machine Learning
url https://arxiv.org/abs/2411.15684