{"entity": "researcher", "timestamp": "2026-08-20T20:47:29.042Z", "family": "Audrey", "given": "Anastasia", "initials": "A", "orcid": "0000-0002-8172-8575", "affiliations": ["Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/436d3f91960447c384d04bf8535b35a9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/436d3f91960447c384d04bf8535b35a9"}}, "publications": [{"entity": "publication", "iuid": "20224117c77c4cf1825278ed9767b7d1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/20224117c77c4cf1825278ed9767b7d1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/20224117c77c4cf1825278ed9767b7d1"}}, "title": "Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets.", "authors": [{"family": "Leo", "given": "Isabelle Rose", "initials": "IR", "orcid": "0000-0002-7627-6690", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21801296760147b78e11b2a0ddcfd0e1.json"}}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Audrey", "given": "Anastasia", "initials": "A", "orcid": "0000-0002-8172-8575", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/436d3f91960447c384d04bf8535b35a9.json"}}, {"family": "Tampere", "given": "Marianna", "initials": "M"}, {"family": "Eirich", "given": "J\u00fcrgen", "initials": "J", "orcid": "0000-0003-0963-1872", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3070defe1f614b57ab391fa9a15c39a2.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/561efcf32e2648c8a10fee692fc4e908.json"}}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95546f158dde40709fbfbb822a8f89c5.json"}}], "type": "journal article", "published": "2025-02-25", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "1948", "issn-l": "2041-1723"}, "abstract": "Proteome-wide profiling has revealed that targeted drugs can have complex protein interaction landscapes. However, it's a challenge to profile drug targets while systematically accounting for the dynamic protein variations that produce populations of multiple proteoforms. We address this problem by combining thermal proteome profiling (TPP) with functional proteoform group detection to refine the target landscape of ibrutinib. In addition to known targets, we implicate additional specific functional proteoform groups linking ibrutinib to mechanisms in immunomodulation and cellular processes like Golgi trafficking, endosomal trafficking, and glycosylation. Further, we identify variability in functional proteoform group profiles in a CLL cohort, linked to treatment status and ex vivo response and resistance. This offers deeper insights into the impacts of functional proteoform groups in a clinical treatment setting and suggests complex biological effects linked to off-target engagement. These results provide a framework for interpreting clinically observed off-target processes and adverse events, highlighting the importance of functional proteoform group-level deconvolution in understanding drug interactions and their functional impacts with potential applications in precision medicine.", "doi": "10.1038/s41467-024-54654-8", "pmid": "40000607", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11862126"}, {"db": "pii", "key": "10.1038/s41467-024-54654-8"}], "notes": [], "created": "2026-08-20T08:53:42.430Z", "modified": "2026-08-20T08:53:42.664Z"}, {"entity": "publication", "iuid": "292b6c1981dd454a9db47e7dd46315f2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/292b6c1981dd454a9db47e7dd46315f2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/292b6c1981dd454a9db47e7dd46315f2"}}, "title": "Deep thermal profiling for detection of functional proteoform groups.", "authors": [{"family": "Kurzawa", "given": "Nils", "initials": "N", "orcid": "0000-0002-7846-2817", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/082e8989ae6e4d61bea479a19a0f0de3.json"}}, {"family": "Leo", "given": "Isabelle Rose", "initials": "IR"}, {"family": "Stahl", "given": "Matthias", "initials": "M"}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Becher", "given": "Isabelle", "initials": "I"}, {"family": "Audrey", "given": "Anastasia", "initials": "A", "orcid": "0000-0002-8172-8575", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/436d3f91960447c384d04bf8535b35a9.json"}}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Huber", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-0474-2218", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/138102f5e406446a8b5f9c421ea1e595.json"}}, {"family": "Mateus", "given": "Andr\u00e9", "initials": "A", "orcid": "0000-0001-6870-0677", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ebf0d242aa894a66b60828456bbc22aa.json"}}, {"family": "Savitski", "given": "Mikhail M", "initials": "MM", "orcid": "0000-0003-2011-9247", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/374222bd4bce42f282690629b9679628.json"}}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95546f158dde40709fbfbb822a8f89c5.json"}}], "type": "journal article", "published": "2023-08-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "19", "issue": "8", "pages": "962-971", "issn-l": "1552-4450"}, "abstract": "The complexity of the functional proteome extends considerably beyond the coding genome, resulting in millions of proteoforms. Investigation of proteoforms and their functional roles is important to understand cellular physiology and its deregulation in diseases but challenging to perform systematically. Here we applied thermal proteome profiling with deep peptide coverage to detect functional proteoform groups in acute lymphoblastic leukemia cell lines with different cytogenetic aberrations. We detected 15,846 proteoforms, capturing differently spliced, cleaved and post-translationally modified proteins expressed from 9,290 genes. We identified differential co-aggregation of proteoform pairs and established links to disease biology. Moreover, we systematically made use of measured biophysical proteoform states to find specific biomarkers of drug sensitivity. Our approach, thus, provides a powerful and unique tool for systematic detection and functional annotation of proteoform groups.", "doi": "10.1038/s41589-023-01284-8", "pmid": "36941476", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10374440"}, {"db": "pii", "key": "10.1038/s41589-023-01284-8"}], "notes": [], "created": "2026-08-20T09:01:33.664Z", "modified": "2026-08-20T09:01:33.770Z"}]}