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Article ; Online: DIAgui: a Shiny application to process the output from DIA-NN.

Gerault, Marc-Antoine / Camoin, Luc / Granjeaud, Samuel

Bioinformatics advances

2024 Volume 4, Issue 1, Page(s) vbae001

Abstract: Summary: DIAgui is an R package to simplify the processing of the report file from the DIA-NN software thanks to a Shiny application. It returns the quantification of either the precursors, the peptides, the proteins, or the genes thanks to the MaxLFQ ... ...

Abstract	Summary: DIAgui is an R package to simplify the processing of the report file from the DIA-NN software thanks to a Shiny application. It returns the quantification of either the precursors, the peptides, the proteins, or the genes thanks to the MaxLFQ algorithm. In addition, the latest version provides the Top3 and iBAQ quantification and the number of peptides used for the quantification. In the end, DIAgui produces ready-to-interpret files from the results of DIA mass spectrometry analysis and provides visualization and statistical tools that can be used in a user-friendly way. Availability and implementation: Code and documentation are available on GitHub at https://github.com/marseille-proteomique/DIAgui. The package is written in R and also uses C++ code. A vignette shows its use in an R command line workflow.
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ISSN	2635-0041
ISSN (online)	2635-0041
DOI	10.1093/bioadv/vbae001
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Article ; Online: Poly-pharmacology of existing drugs: How to crack the code?

Mouysset, Baptiste / Le Grand, Marion / Camoin, Luc / Pasquier, Eddy

Cancer letters

2024 Volume 588, Page(s) 216800

Abstract: Drug development in oncology is highly challenging, with less than 5% success rate in clinical trials. This alarming figure points out the need to study in more details the multiple biological effects of drugs in specific contexts. Indeed, the ... ...

Abstract	Drug development in oncology is highly challenging, with less than 5% success rate in clinical trials. This alarming figure points out the need to study in more details the multiple biological effects of drugs in specific contexts. Indeed, the comprehensive assessment of drug poly-pharmacology can provide insights into their therapeutic and adverse effects, to optimize their utilization and maximize the success rate of clinical trials. Recent technological advances have made possible in-depth investigation of drug poly-pharmacology. This review first highlights high-throughput methodologies that have been used to unveil new mechanisms of action of existing drugs. Then, we discuss how emerging chemo-proteomics strategies allow effectively dissecting the poly-pharmacology of drugs in an unsupervised manner.
MeSH term(s)	Humans ; Proteomics ; Neoplasms/drug therapy ; Polypharmacy
Language	English
Publishing date	2024-03-14
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2024.216800
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Article ; Online: IMPRINTS.CETSA and IMPRINTS.CETSA.app: an R package and a Shiny application for the analysis and interpretation of IMPRINTS-CETSA data.

Gerault, Marc-Antoine / Granjeaud, Samuel / Camoin, Luc / Nordlund, Pär / Dai, Lingyun

Briefings in bioinformatics

2024 Volume 25, Issue 3

Abstract: IMPRINTS-CETSA (Integrated Modulation of Protein Interaction States-Cellular Thermal Shift Assay) provides a highly resolved means to systematically study the interactions of proteins with other cellular components, including metabolites, nucleic acids ... ...

Abstract	IMPRINTS-CETSA (Integrated Modulation of Protein Interaction States-Cellular Thermal Shift Assay) provides a highly resolved means to systematically study the interactions of proteins with other cellular components, including metabolites, nucleic acids and other proteins, at the proteome level, but no freely available and user-friendly data analysis software has been reported. Here, we report IMPRINTS.CETSA, an R package that provides the basic data processing framework for robust analysis of the IMPRINTS-CETSA data format, from preprocessing and normalization to visualization. We also report an accompanying R package, IMPRINTS.CETSA.app, which offers a user-friendly Shiny interface for analysis and interpretation of IMPRINTS-CETSA results, with seamless features such as functional enrichment and mapping to other databases at a single site. For the hit generation part, the diverse behaviors of protein modulations have been typically segregated with a two-measure scoring method, i.e. the abundance and thermal stability changes. We present a new algorithm to classify modulated proteins in IMPRINTS-CETSA experiments by a robust single-measure scoring. In this way, both the numerical changes and the statistical significances of the IMPRINTS information can be visualized on a single plot. The IMPRINTS.CETSA and IMPRINTS.CETSA.app R packages are freely available on GitHub at https://github.com/nkdailingyun/IMPRINTS.CETSA and https://github.com/mgerault/IMPRINTS.CETSA.app, respectively. IMPRINTS.CETSA.app is also available as an executable program at https://zenodo.org/records/10636134.
MeSH term(s)	Mobile Applications ; Software ; Proteome ; Algorithms ; Research Design
Chemical Substances	Proteome
Language	English
Publishing date	2024-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2068142-2
ISSN	1477-4054 ; 1467-5463
ISSN (online)	1477-4054
ISSN	1467-5463
DOI	10.1093/bib/bbae128
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Article ; Online: Insights into the modes of action of tritium on the early-life stages of zebrafish, Danio rerio, using transcriptomic and proteomic analyses.

Arcanjo, Caroline / Frelon, Sandrine / Armant, Olivier / Camoin, Luc / Audebert, Stéphane / Camilleri, Virginie / Cavalié, Isabelle / Adam-Guillermin, Christelle / Gagnaire, Beatrice

Journal of environmental radioactivity

2023 Volume 261, Page(s) 107141

Abstract: In the environment, populations are exposed to different kinds of ionizing radiation. Little is known about their modes of action on non-human species, and whether or not they are similar for alpha, beta and gamma radiations, considered as the reference. ...

Abstract	In the environment, populations are exposed to different kinds of ionizing radiation. Little is known about their modes of action on non-human species, and whether or not they are similar for alpha, beta and gamma radiations, considered as the reference. In this context, tritium effects (beta emitter) under the form of tritiated water (HTO) were investigated in zebrafish, a common model in toxicology and ecotoxicology with a fully sequenced genome. Experiments were conducted on early life stages, considered to be highly sensitive to pollutants, by exposing eggs to 0.4 mGy/h of HTO until 10 days post fertilization. Tritium internalization was quantified, and effects were investigated using a combined approach of transcriptomic and proteomic analyses. Results highlighted similarities in the biological pathways affected by HTO by both techniques, such as defence response, muscle integrity and contraction, and potential visual alterations. These results correlated well with previous data obtained on earlier developmental stages (1 and 4 dpf). Interestingly, HTO effects were partly overlapping those obtained after gamma irradiation, underlying potential common modes of action. This study, therefore, brought a body of evidence on the effects of HTO observed at the molecular level on zebrafish larvae. Further studies could investigate if the effects persist in adult organisms.
MeSH term(s)	Animals ; Zebrafish/metabolism ; Transcriptome ; Tritium/metabolism ; Proteomics ; Radiation Monitoring ; Larva/metabolism ; Water Pollutants, Chemical/metabolism
Chemical Substances	Tritium (10028-17-8) ; Water Pollutants, Chemical
Language	English
Publishing date	2023-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	1483112-0
ISSN	1879-1700 ; 0265-931X
ISSN (online)	1879-1700
ISSN	0265-931X
DOI	10.1016/j.jenvrad.2023.107141
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Article ; Online: A vertebrate Vangl2 translational variant required for planar cell polarity.

Walton, Alexandra / Thomé, Virginie / Revinski, Diego / Marchetto, Sylvie / Puvirajesinghe, Tania M / Audebert, Stéphane / Camoin, Luc / Bailly, Eric / Kodjabachian, Laurent / Borg, Jean-Paul

The Journal of biological chemistry

2024 Volume 300, Issue 4, Page(s) 106792

Abstract: First described in the milkweed bug Oncopeltus fasciatus, planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily ... ...

Abstract	First described in the milkweed bug Oncopeltus fasciatus, planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily conserved genes encoding transmembrane (Vangl, Frizzled, Celsr) and cytoplasmic (Prickle, Dishevelled) molecules. Vangl2 is of major importance in embryonic development as illustrated by its pivotal role during neural tube closure in human, mouse, Xenopus, and zebrafish embryos. Here, we report on the molecular and functional characterization of a Vangl2 isoform, Vangl2-Long, containing an N-terminal extension of about 50 aa, which arises from an alternative near-cognate AUA translation initiation site, lying upstream of the conventional start codon. While missing in Vangl1 paralogs and in all invertebrates, including Drosophila, this N-terminal extension is conserved in all vertebrate Vangl2 sequences. We show that Vangl2-Long belongs to a multimeric complex with Vangl1 and Vangl2. Using morpholino oligonucleotides to specifically knockdown Vangl2-Long in Xenopus, we found that this isoform is functional and required for embryo extension and neural tube closure. Furthermore, both Vangl2 and Vangl2-Long must be correctly expressed for the polarized distribution of the PCP molecules Pk2 and Dvl1 and for centriole rotational polarity in ciliated epidermal cells. Altogether, our study suggests that Vangl2-Long significantly contributes to the pool of Vangl2 molecules present at the plasma membrane to maintain PCP in vertebrate tissues.
MeSH term(s)	Cell Polarity ; Animals ; Dishevelled Proteins/metabolism ; Dishevelled Proteins/genetics ; Humans ; Xenopus Proteins/metabolism ; Xenopus Proteins/genetics ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; Mice ; Nerve Tissue Proteins/metabolism ; Nerve Tissue Proteins/genetics ; Protein Isoforms/metabolism ; Protein Isoforms/genetics ; Zebrafish Proteins/metabolism ; Zebrafish Proteins/genetics ; Zebrafish/metabolism ; Zebrafish/genetics ; Xenopus laevis ; Protein Biosynthesis ; Carrier Proteins ; Intracellular Signaling Peptides and Proteins
Chemical Substances	Dishevelled Proteins ; VANGL2 protein, human ; Xenopus Proteins ; Membrane Proteins ; Nerve Tissue Proteins ; vangl2 protein, zebrafish ; Protein Isoforms ; Vangl2 protein, Xenopus ; DVL1 protein, Xenopus ; Zebrafish Proteins ; DVL1 protein, human ; VANGL1 protein, human ; Ltap protein, mouse ; Vangl1 protein, mouse ; Carrier Proteins ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2024-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2024.106792
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Article ; Online: The Scribble family in cancer: twentieth anniversary.

Santoni, Marie-Josée / Kashyap, Rudra / Camoin, Luc / Borg, Jean-Paul

Oncogene

2020 Volume 39, Issue 47, Page(s) 7019–7033

Abstract: Among the more than 160 PDZ containing proteins described in humans, the cytoplasmic scaffold Scribble stands out because of its essential role in many steps of cancer development and dissemination. Its fame has somehow blurred the importance of ... ...

Abstract	Among the more than 160 PDZ containing proteins described in humans, the cytoplasmic scaffold Scribble stands out because of its essential role in many steps of cancer development and dissemination. Its fame has somehow blurred the importance of homologous proteins, Erbin and Lano, all belonging to the LRR and PDZ (LAP) protein family first described twenty years ago. In this review, we will retrace the history of LAP family protein research and draw attention to their contribution in cancer by detailing the features of its members at the structural and functional levels, and highlighting their shared-but also different-implication in the tumoral process.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Amino Acid Sequence ; Animals ; Caenorhabditis elegans Proteins/genetics ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Disease Models, Animal ; Drosophila Proteins/genetics ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Neoplasms/pathology ; Protein Domains/genetics ; Protein Interaction Maps ; Protein Processing, Post-Translational ; Sequence Homology, Amino Acid ; Sialoglycoproteins/genetics ; Sialoglycoproteins/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Caenorhabditis elegans Proteins ; Carrier Proteins ; Drosophila Proteins ; ERBIN protein, human ; LET-413 protein, C elegans ; LRRC1 protein, human ; LRRC7 protein, human ; Membrane Proteins ; SCRIB protein, human ; Scrib protein, Drosophila ; Sialoglycoproteins ; Tumor Suppressor Proteins
Keywords	covid19
Language	English
Publishing date	2020-09-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-020-01478-7
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Article ; Online: Identification of PDZ Interactions by Affinity Purification and Mass Spectrometry Analysis.

Daulat, Avais M / Audebert, Stéphane / Wagner, Mônica / Camoin, Luc / Borg, Jean-Paul

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2256, Page(s) 17–40

Abstract: Identification of protein networks becomes indispensable for determining the function of a given protein of interest. Some proteins harbor a PDZ binding motif (PDZBM) located at the carboxy-terminus end. This motif is necessary to recruit PDZ domain ... ...

Abstract	Identification of protein networks becomes indispensable for determining the function of a given protein of interest. Some proteins harbor a PDZ binding motif (PDZBM) located at the carboxy-terminus end. This motif is necessary to recruit PDZ domain proteins which are involved in signaling, trafficking, and maintenance of cell architecture. In the present chapter, we present two complementary approaches (immunopurification and peptide-based purification procedures) followed by mass spectrometry analysis to identify PDZ domain proteins associated to a given protein of interest. As proof of example, we focus our attention on TANC1 which is a scaffold protein harboring a PDZBM at its carboxy-terminus. Using these two approaches, we identified several PDZ domain containing proteins. Some of them were found with both approaches, and some were specifically identified using peptide-based purification procedure. This exemplifies advantages and differences of both strategies to identify PDZ interactions.
MeSH term(s)	Chromatography, Affinity/methods ; HEK293 Cells ; Humans ; Mass Spectrometry/methods ; Membrane Proteins/metabolism ; PDZ Domains ; Protein Binding
Chemical Substances	Membrane Proteins ; TANC1 protein, human
Language	English
Publishing date	2021-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1166-1_2
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Article ; Online: Targeting NUPR1-dependent stress granules formation to induce synthetic lethality in Kras

Santofimia-Castaño, Patricia / Fraunhoffer, Nicolas / Liu, Xi / Bessone, Ivan Fernandez / di Magliano, Marina Pasca / Audebert, Stephane / Camoin, Luc / Estaras, Matias / Brenière, Manon / Modesti, Mauro / Lomberk, Gwen / Urrutia, Raul / Soubeyran, Philippe / Neira, Jose Luis / Iovanna, Juan

EMBO molecular medicine

2024 Volume 16, Issue 3, Page(s) 475–505

Abstract: We find that NUPR1, a stress-associated intrinsically disordered protein, induced droplet formation via liquid-liquid phase separation (LLPS). NUPR1-driven LLPS was crucial for the creation of NUPR1-dependent stress granules (SGs) in pancreatic cancer ... ...

Abstract	We find that NUPR1, a stress-associated intrinsically disordered protein, induced droplet formation via liquid-liquid phase separation (LLPS). NUPR1-driven LLPS was crucial for the creation of NUPR1-dependent stress granules (SGs) in pancreatic cancer cells since genetic or pharmacological inhibition by ZZW-115 of NUPR1 activity impeded SGs formation. The Kras
MeSH term(s)	Animals ; Mice ; Carcinoma in Situ/genetics ; Carcinoma in Situ/metabolism ; Carcinoma in Situ/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Caspase 3/genetics ; Caspase 3/metabolism ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Piperazines ; Proto-Oncogene Proteins p21(ras)/genetics ; Stress Granules ; Synthetic Lethal Mutations ; Thiazines
Chemical Substances	Caspase 3 (EC 3.4.22.-) ; NUPR1 inhibitor ZZW-115 ; Piperazines ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Thiazines ; Nupr1 protein, mouse ; Hras protein, mouse (EC 3.6.5.2)
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.1038/s44321-024-00032-2
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Article ; Online: Direct capture, inhibition and crystal structure of HsaD (Rv3569c) from M. tuberculosis

Barelier, Sarah / Avellan, Romain / Gnawali, Giri Raj / Fourquet, Patrick / Roig‐Zamboni, Véronique / Poncin, Isabelle / Point, Vanessa / Bourne, Yves / Audebert, Stéphane / Camoin, Luc / Spilling, Christopher D. / Canaan, Stéphane / Cavalier, Jean‐François / Sulzenbacher, Gerlind

The FEBS Journal. 2023 Mar., v. 290, no. 6 p.1563-1582

2023

Abstract: A hallmark of Mycobacterium tuberculosis (M. tb), the aetiologic agent of tuberculosis, is its ability to metabolise host‐derived lipids. However, the enzymes and mechanisms underlying such metabolism are still largely unknown. We previously reported ... ...

Abstract	A hallmark of Mycobacterium tuberculosis (M. tb), the aetiologic agent of tuberculosis, is its ability to metabolise host‐derived lipids. However, the enzymes and mechanisms underlying such metabolism are still largely unknown. We previously reported that the Cyclophostin & Cyclipostins (CyC) analogues, a new family of potent antimycobacterial molecules, react specifically and covalently with (Ser/Cys)‐based enzymes mostly involved in bacterial lipid metabolism. Here, we report the synthesis of new CyC alkyne‐containing inhibitors (CyCyₙₑ) and their use for the direct fishing of target proteins in M. tb culture via bio‐orthogonal click‐chemistry activity‐based protein profiling (CC‐ABPP). This approach led to the capture and identification of a variety of enzymes, and many of them involved in lipid or steroid metabolisms. One of the captured enzymes, HsaD (Rv3569c), is required for the survival of M. tb within macrophages and is thus a potential therapeutic target. This prompted us to further explore and validate, through a combination of biochemical and structural approaches, the specificity of HsaD inhibition by the CyC analogues. We confirmed that the CyC bind covalently to the catalytic Ser¹¹⁴ residue, leading to a total loss of enzyme activity. These data were supported by the X‐ray structures of four HsaD‐CyC complexes, obtained at resolutions between 1.6 and 2.6 Å. The identification of mycobacterial enzymes directly captured by the CyCyₙₑ probes through CC‐ABPP paves the way to better understand and potentially target key players at crucial stages of the bacilli life cycle.
Keywords	Mycobacterium tuberculosis ; X-radiation ; chemical bonding ; crystal structure ; enzyme activity ; etiological agents ; lipid metabolism ; lipids ; macrophages ; new family ; therapeutics ; tuberculosis
Language	English
Dates of publication	2023-03
Size	p. 1563-1582.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16645
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Article ; Online: Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway.

Ruminski, Kilian / Celis-Gutierrez, Javier / Jarmuzynski, Nicolas / Maturin, Emilie / Audebert, Stephane / Malissen, Marie / Camoin, Luc / Voisinne, Guillaume / Malissen, Bernard / Roncagalli, Romain

Frontiers in immunology

2023 Volume 14, Page(s) 1139123

Abstract: The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein- ... ...

Abstract	The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic perturbations is critical to understand the resulting phenotypes. Here, by combining genome editing techniques in T cells and interactomics studies based on affinity purification coupled to mass spectrometry (AP-MS) analysis, we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the ablation of each of the three GRB2-family adaptors. Our data showed that the absence of GADS or GRB2 induces a major remodeling of the PPI network associated with SLP76 following TCR engagement. Unexpectedly, this PPI network rewiring minimally affects proximal molecular events of the TCR signaling pathway. Nevertheless, during prolonged TCR stimulation, GRB2- and GADS-deficient cells displayed a reduced level of activation and cytokine secretion capacity. Using the canonical SLP76 signalosome, this analysis highlights the plasticity of PPI networks and their reorganization following specific genetic perturbations.
MeSH term(s)	T-Lymphocytes/metabolism ; Signal Transduction/genetics ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Protein Interaction Maps
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1139123
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