PXD044934-1

PXD044934 is an original dataset announced via ProteomeXchange.

Title	InstaNovo enables diffusion-powered de novo peptide identification in large scale proteomics experiments
Description	Bottom-up mass spectrometry-based proteomics is challenged by the task of identifying the peptide that generates a tandem mass spectrum. Traditional methods that rely on known peptide sequence databases are limited and may not be applicable in certain contexts. De novo peptide sequencing, which assigns peptide sequences to the spectra without prior information, is valuable for various biological applications; yet, due to a lack of accuracy, it remains challenging to apply this approach in many situations. Here, we introduce InstaNovo, a transformer neural network with the ability to translate fragment ion peaks into the sequence of amino acids that make up the studied peptide(s). The model was trained on 28 million labelled spectra matched to ~742k human peptides from the ProteomeTools project. We demonstrate that InstaNovo outperforms current state-of-the-art methods on benchmark datasets and showcase its utility in several applications. Building upon human intuition, we also introduce InstaNovo+, a multinomial diffusion model that further improves performance by iterative refinement of predicted sequences. Using these models, we could de novo sequence antibody-based therapeutics with unprecedented coverage, discover novel peptides, and detect unreported organisms in different datasets, thereby expanding the scope and detection rate of proteomics searches. Finally, we could experimentally validate tryptic and non-tryptic peptides with targeted proteomics, demonstrating the fidelity of our predictions.
HostingRepository	PRIDE
AnnounceDate	2025-01-07
AnnouncementXML	Submission_2025-01-07_02:20:57.889.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Konstantinos Kalogeropoulos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Eclipse; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-29 09:29:34	ID requested
⏵ 1	2025-01-07 02:20:58	announced

Dataset with its publication pending

submitter keyword: peptidomics, machine learning, protein sequencing,proteomics, de novo sequencing

Timothy Patrick
contact affiliation	DTU Bioengineering
contact email	tpaje@dtu.dk
lab head
Konstantinos Kalogeropoulos
contact affiliation	Technical University of Denmark
contact email	konskalogero@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044934
     1. Label: PRIDE project
     2. Name: InstaNovo enables diffusion-powered de novo peptide identification in large scale proteomics experiments