{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:46:36Z","timestamp":1781808396183,"version":"3.54.5"},"reference-count":51,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206211\/Z\/17\/Z"],"award-info":[{"award-number":["206211\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203149"],"award-info":[{"award-number":["203149"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["mcponline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular & Cellular Proteomics"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1016\/j.mcpro.2021.100169","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T23:35:47Z","timestamp":1635982547000},"page":"100169","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"title":["Low Cell Number Proteomic Analysis Using In-Cell Protease Digests Reveals a Robust Signature for Cell Cycle State Classification"],"prefix":"10.1016","volume":"21","author":[{"given":"Van","family":"Kelly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymen","family":"al-Rawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-0866","authenticated-orcid":false,"given":"Georg","family":"Kustatscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-5215","authenticated-orcid":false,"given":"Tony","family":"Ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mcpro.2021.100169_bib1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.27574","article-title":"Proteomic analysis of cell cycle progression in asynchronous cultures, including mitotic subphases, using PRIMMUS","volume":"6","author":"Ly","year":"2017","journal-title":"Elife"},{"key":"10.1016\/j.mcpro.2021.100169_bib2","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.04534","article-title":"Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells","volume":"4","author":"Ly","year":"2015","journal-title":"Elife"},{"key":"10.1016\/j.mcpro.2021.100169_bib3","article-title":"Proteomic analysis of cell cycle progression in asynchronous cultures, including mitotic subphases, using PRIMMUS","author":"Ly","year":"2017","journal-title":"bioRxiv"},{"key":"10.1016\/j.mcpro.2021.100169_bib4","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1074\/mcp.R120.002234","article-title":"Single-cell proteomics: Progress and prospects","volume":"19","author":"Kelly","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mcpro.2021.100169_bib5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13059-021-02267-5","article-title":"Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity using SCoPE2","volume":"22","author":"Specht","year":"2021","journal-title":"Genome Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wi\u015bniewski","year":"2009","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mcpro.2021.100169_bib7","doi-asserted-by":"crossref","first-page":"757","DOI":"10.15252\/msb.20145625","article-title":"Ultrasensitive proteome analysis using paramagnetic bead technology","volume":"10","author":"Hughes","year":"2014","journal-title":"Mol. Syst. Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib8","doi-asserted-by":"crossref","first-page":"5554","DOI":"10.1021\/acs.analchem.0c00470","article-title":"Miniaturized filter-aided sample preparation (MICRO-FASP) method for high throughput, ultrasensitive proteomics sample preparation reveals proteome asymmetry in Xenopus laevis embryos","volume":"92","author":"Zhang","year":"2020","journal-title":"Anal. Chem."},{"key":"10.1016\/j.mcpro.2021.100169_bib9","article-title":"Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation","author":"Brunner","year":"2021","journal-title":"bioRxiv"},{"key":"10.1016\/j.mcpro.2021.100169_bib10","article-title":"An automated workflow for label-free and multiplexed single cell proteomics sample preparation at unprecedented sensitivity","author":"Hartlmayr","year":"2021","journal-title":"bioRxiv"},{"key":"10.1016\/j.mcpro.2021.100169_bib11","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/s41467-018-03367-w","article-title":"Nanodroplet processing platform for deep and quantitative proteome profiling of 10\u2013100 mammalian cells","volume":"9","author":"Zhu","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mcpro.2021.100169_bib12","doi-asserted-by":"crossref","first-page":"6235","DOI":"10.1074\/jbc.M310752200","article-title":"Identification of formaldehyde-induced modifications in proteins: Reactions with model peptides","volume":"279","author":"Metz","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.mcpro.2021.100169_bib13","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.aca.2008.04.049","article-title":"Mass spectrometric identification of formaldehyde-induced peptide modifications under in\u00a0vivo protein cross-linking conditions","volume":"618","author":"Toews","year":"2008","journal-title":"Anal. Chim. Acta"},{"key":"10.1016\/j.mcpro.2021.100169_bib14","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0006-291X(78)90185-7","article-title":"Isolation of a human lymphoblastoid line heterozygous at the thymidine kinase locus: Possibility for a rapid human cell mutation assay","volume":"84","author":"Skopek","year":"1978","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.mcpro.2021.100169_bib15","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.mcpro.2021.100169_bib16","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nprot.2016.020","article-title":"Rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) for analysis of chromatin complexes","volume":"11","author":"Mohammed","year":"2016","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.mcpro.2021.100169_bib17","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1038\/nprot.2016.136","article-title":"The MaxQuant computational platform for mass spectrometry-based shotgun proteomics","volume":"11","author":"Tyanova","year":"2016","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.mcpro.2021.100169_bib18","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2144\/04374RV01","article-title":"Proteomic analyses using an accurate mass and time tag strategy","volume":"37","author":"Pasa-Toli\u0107","year":"2004","journal-title":"Biotechniques"},{"key":"10.1016\/j.mcpro.2021.100169_bib19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41592-018-0003-5","article-title":"BoxCar acquisition method enables single-shot proteomics at a depth of 10,000 proteins in 100 minutes","volume":"15","author":"Meier","year":"2018","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mcpro.2021.100169_bib20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/10049","article-title":"Temporal and spatial control of cyclin B1 destruction in metaphase","volume":"1","author":"Clute","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1083\/jcb.153.1.121","article-title":"Cyclin a is destroyed in prometaphase and can delay chromosome alignment and anaphase","volume":"153","author":"Elzen den","year":"2001","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib22","doi-asserted-by":"crossref","first-page":"70323","DOI":"10.18632\/oncotarget.11855","article-title":"ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication","volume":"7","author":"Koo","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.mcpro.2021.100169_bib23","first-page":"D296","article-title":"ELM\u2014the eukaryotic linear motif resource in 2020","volume":"48","author":"Kumar","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.mcpro.2021.100169_bib24","doi-asserted-by":"crossref","first-page":"287048","DOI":"10.1155\/2015\/287048","article-title":"Posttranscriptional regulation of splicing factor SRSF1 and its role in cancer cell biology","volume":"2015","author":"Gon\u00e7alves","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.mcpro.2021.100169_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0059137","article-title":"Proteasome-mediated proteolysis of SRSF5 splicing factor intriguingly co-occurs with SRSF5 mRNA upregulation during late erythroid differentiation","volume":"8","author":"Breig","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.mcpro.2021.100169_bib26","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a012716","article-title":"DNA damage sensing by the ATM and ATR kinases","volume":"5","author":"Mar\u00e9chal","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib27","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.bbamcr.2018.09.011","article-title":"Who guards the guardian? Mechanisms that restrain APC\/C during the cell cycle","volume":"1865","author":"Kernan","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"10.1016\/j.mcpro.2021.100169_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sbi.2014.08.003","article-title":"Insights into the anaphase-promoting complex: A molecular machine that regulates mitosis","volume":"29","author":"Chang","year":"2014","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.molcel.2016.09.006","article-title":"Building a regulatory network with short linear sequence motifs: Lessons from the degrons of the anaphase-promoting complex","volume":"64","author":"Davey","year":"2016","journal-title":"Mol. Cell"},{"key":"10.1016\/j.mcpro.2021.100169_bib30","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.devcel.2015.01.003","article-title":"The ABBA motif binds APC\/C activators and is shared by APC\/C substrates and regulators","volume":"32","author":"Di Fiore","year":"2015","journal-title":"Dev. Cell"},{"key":"10.1016\/j.mcpro.2021.100169_bib31","doi-asserted-by":"crossref","first-page":"4332","DOI":"10.1242\/jcs.094763","article-title":"BubR1 blocks substrate recruitment to the APC\/C in a KEN-box-dependent manner","volume":"124","author":"Lara-Gonzalez","year":"2011","journal-title":"J.\u00a0Cell Sci."},{"key":"10.1016\/j.mcpro.2021.100169_bib32","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41586-020-2182-3","article-title":"Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2","volume":"580","author":"Hellmuth","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.mcpro.2021.100169_bib33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrg3833","article-title":"Computational and analytical challenges in single-cell transcriptomics","volume":"16","author":"Stegle","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.mcpro.2021.100169_bib34","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ymeth.2015.06.021","article-title":"Computational assignment of cell-cycle stage from single-cell transcriptome data","volume":"85","author":"Scialdone","year":"2015","journal-title":"Methods"},{"key":"10.1016\/j.mcpro.2021.100169_bib35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41467-017-00039-z","article-title":"Reconstructing cell cycle pseudo time-series via single-cell transcriptome data","volume":"8","author":"Liu","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mcpro.2021.100169_bib36","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/s41467-020-14457-z","article-title":"Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression","volume":"11","author":"Cuomo","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mcpro.2021.100169_bib37","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.01630","article-title":"A\u00a0proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells","volume":"3","author":"Ly","year":"2014","journal-title":"Elife"},{"key":"10.1016\/j.mcpro.2021.100169_bib38","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/s41587-019-0298-5","article-title":"Co-regulation map of the human proteome enables identification of protein functions","volume":"37","author":"Kustatscher","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.mcpro.2021.100169_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0080425","article-title":"Dynamic impacts of the inhibition of the molecular chaperone Hsp90 on the T-cell proteome have implications for anti-cancer therapy","volume":"8","author":"Fierro-Monti","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.mcpro.2021.100169_bib40","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1074\/mcp.TIR118.001270","article-title":"Protein aggregation capture on microparticles enables multipurpose proteomics sample preparation","volume":"18","author":"Batth","year":"2019","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mcpro.2021.100169_bib41","doi-asserted-by":"crossref","first-page":"100077","DOI":"10.1016\/j.mcpro.2021.100077","article-title":"IonQuant enables accurate and sensitive label-free quantification with FDR-controlled match-between-runs","volume":"20","author":"Yu","year":"2021","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mcpro.2021.100169_bib42","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1074\/mcp.RA119.001857","article-title":"An improved boosting to amplify signal with isobaric labeling (iBASIL) strategy for precise quantitative single-cell proteomics","volume":"19","author":"Tsai","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mcpro.2021.100169_bib43","doi-asserted-by":"crossref","DOI":"10.1126\/science.aan2507","article-title":"A\u00a0pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.mcpro.2021.100169_bib44","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/ncb2918","article-title":"Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components","volume":"16","author":"Alabert","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005554","article-title":"Uncovering hidden layers of cell cycle regulation through integrative multi-omic analysis","volume":"11","author":"Aviner","year":"2015","journal-title":"PLoS Genet."},{"key":"10.1016\/j.mcpro.2021.100169_bib46","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41586-021-03232-9","article-title":"Spatiotemporal dissection of the cell cycle with single-cell proteogenomics","volume":"590","author":"Mahdessian","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.mcpro.2021.100169_bib47","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1074\/mcp.RA120.001938","article-title":"Cell cycle profiling reveals protein oscillation, phosphorylation, and localization dynamics","volume":"19","author":"Herr","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mcpro.2021.100169_bib48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000975","article-title":"In silico APC\/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators","volume":"18","author":"Franks","year":"2020","journal-title":"PLoS Biol."},{"key":"10.1016\/j.mcpro.2021.100169_bib49","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1038\/s41467-018-07251-5","article-title":"An E2-ubiquitin thioester-driven approach to identify substrates modified with ubiquitin and ubiquitin-like molecules","volume":"9","author":"Bakos","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mcpro.2021.100169_bib50","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1074\/mcp.RA120.002069","article-title":"The insulin receptor adaptor IRS2 is an APC\/C substrate that promotes cell cycle protein expression and a robust spindle assembly checkpoint","volume":"19","author":"Manohar","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mcpro.2021.100169_bib51","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1038\/s41467-020-16935-w","article-title":"Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins","volume":"11","author":"Tayri-Wilk","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Molecular & Cellular Proteomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1535947621001419?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1535947621001419?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:24:25Z","timestamp":1778617465000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1535947621001419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["S1535947621001419"],"URL":"https:\/\/doi.org\/10.1016\/j.mcpro.2021.100169","relation":{},"ISSN":["1535-9476"],"issn-type":[{"value":"1535-9476","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Low Cell Number Proteomic Analysis Using In-Cell Protease Digests Reveals a Robust Signature for Cell Cycle State Classification","name":"articletitle","label":"Article Title"},{"value":"Molecular & Cellular Proteomics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mcpro.2021.100169","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"100169"}}