| 1. |
- Demichev, Vadim, et al.
(author)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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In: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Journal article (peer-reviewed)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 2. |
- Lorenzi, Arthur, et al.
(author)
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MoCCA : A Model of Comparative Concepts for Aligning Constructicons
- 2024
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In: ISA 2024. - : European Language Resources Association. - 9782493814326 ; , s. 93-98
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Conference paper (peer-reviewed)abstract
- This paper presents MoCCA, a Model of Comparative Concepts for Aligning Constructicons under development by a consortium of research groups building Constructicons of different languages including Brazilian Portuguese, English, German and Swedish. The Constructicons will be aligned by using comparative concepts (CCs) providing language-neutral definitions of linguistic properties. The CCs are drawn from typological research on grammatical categories and constructions, and from FrameNet frames, organized in a conceptual network. Language-specific constructions are linked to the CCs in accordance with general principles. MoCCA is organized into files of two types: a largely static CC Database file and multiple Linking files containing relations between constructions in a Constructicon and the CCs. Tools are planned to facilitate visualization of the CC network and linking of constructions to the CCs. All files and guidelines will be versioned, and a mechanism is set up to report cases where a language-specific construction cannot be easily linked to existing CCs. © 2024 ELRA Language Resource Association: CC BY-NC 4.0.
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| 3. |
- Lorenzi, Arthur, et al.
(author)
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MoCCA: A Model of Comparative Concepts for Aligning Constructicons
- 2024
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In: Proceedings of the 20th Joint ACL - ISO Workshop on Interoperable Semantic Annotation @LREC-COLING-2024, 20 May, 2024, Torino, Italia. - : ELRA. - 2522-2686. - 9782493814326
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Conference paper (peer-reviewed)abstract
- This paper presents MoCCA, a Model of Comparative Concepts for Aligning Constructicons under development by a consortium of research groups building Constructicons of different languages including Brazilian Portuguese, English, German and Swedish. The Constructicons will be aligned by using comparative concepts (CCs) providing language-neutral definitions of linguistic properties. The CCs are drawn from typological research on grammatical categories and constructions, and from FrameNet frames, organized in a conceptual network. Language-specific constructions are linked to the CCs in accordance with general principles. MoCCA is organized into files of two types: a largely static CC Database file and multiple Linking files containing relations between constructions in a Constructicon and the CCs. Tools are planned to facilitate visualization of the CC network and linking of constructions to the CCs. All files and guidelines will be versioned, and a mechanism is set up to report cases where a language-specific construction cannot be easily linked to existing CCs.
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| 4. |
- Schöpf, Julia, et al.
(author)
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Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions
- 2024
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In: Nature Communications. - 2041-1723. ; 15, s. 1-17
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Journal article (peer-reviewed)abstract
- Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers.
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