PXD011680 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | De novo sequencing of antibody light chain proteoforms from patients with multiple myeloma |
| Description | In multiple myeloma diseases, monoclonal immunoglobulin light chains (LCs) are abundantly produced, with as a consequence in some cases the formation of deposits affecting various organs, such as kidney, while in other cases to remain soluble up to concentrations of several g.L-1 in plasma. The exact factors crucial for the solubility of light chains are poorly understood, but it can be hypothesized that their amino acid sequence plays an important role. Determining the precise sequences of patient-derived light chains is therefore highly desirable. We establish here a novel de novo sequencing workflow for patient-derived LCs, based on the combination of bottom-up and top-down proteomics without database search. PEAKS is used for the de novo sequencing of peptides that are further assembled into full length LC sequences using ALPS. Top-down proteomics provides the molecular masses of proteoforms and allows the exact determination of the amino acid sequence including all post translational modifications. This pipeline is then used for the complete de novo sequencing of LCs extracted from the urine of 10 patients with multiple myeloma. We show that for the bottom-up part, digestions with trypsin and Nepenthes digestive fluid are sufficient to produce overlapping peptides able to generate the best sequence candidates. Top-down proteomics is absolutely required to achieve 100% final sequence coverage and characterize clinical samples containing several LCs . Our work highlights an unexpected range of modifications. |
| HostingRepository | PRIDE |
| AnnounceDate | 2022-02-14 |
| AnnouncementXML | Submission_2022-02-13_16:19:15.797.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Oleg Klykov |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
| ModificationList | cysteinylation (disulfide with free L-cysteine); iodoacetamide derivatized residue |
| Instrument | Orbitrap Fusion Lumos; Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2018-11-13 05:36:02 | ID requested | |
| 1 | 2020-01-09 10:15:41 | announced | |
| 2 | 2020-01-17 06:12:20 | announced | 2020-01-17: Updated publication reference for PubMed record(s): 31924745. |
| 3 | 2020-02-17 02:25:51 | announced | 2020-01-17: Updated publication reference for PubMed record(s): 31924745.
2020-02-17: Updated publication reference for PubMed record(s): 31924745. |
| 4 | 2020-11-06 08:13:19 | announced | 2020-11-06: Updated project metadata. |
| ⏵ 5 | 2022-02-13 16:19:16 | announced | 2022-02-14: Updated project metadata. |
| 6 | 2022-02-13 16:27:29 | announced | 2022-02-14: Updated project metadata. |
| 7 | 2024-10-22 04:55:08 | announced | 2024-10-22: Updated project metadata. |
Publication List
| Dupr, é M, Duchateau M, Sternke-Hoffmann R, Boquoi A, Malosse C, Fenk R, Haas R, Buell AK, Rey M, Chamot-Rooke J, Sequencing of Antibody Light Chain Proteoforms from Patients with Multiple Myeloma. Anal Chem, 93(30):10627-10634(2021) [pubmed] |
Keyword List
| ProteomeXchange project tag: EPIC-XS |
| submitter keyword: proteoforms, top-down proteomics,antibody, bottom-up proteomics, de novo sequencing, light chain disease |
Contact List
| Albert J. R. Heck |
|---|
| contact affiliation | Distinguished Faculty Professor Utrecht University Scientific Director Netherlands Proteomics Centre and Scientific Director Utrecht Institute for Pharmaceutical Sciences Biomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University Padualaan 8, 3584 CH Utrecht, The Netherlands |
| contact email | A.J.R.Heck@uu.nl |
| lab head | |
| Oleg Klykov |
|---|
| contact affiliation | Utrecht University |
| contact email | o.klykov@uu.nl |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD011680 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD011680
- Label: PRIDE project
- Name: De novo sequencing of antibody light chain proteoforms from patients with multiple myeloma
to receive all new ProteomeXchange dataset release announcements!
