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Article ; Online: Complex Networks in Health and Disease

Vulliard, Loan / Menche, Jörg

Reference Module in Biomedical Sciences

Abstract: From protein interactions to signal transduction, from metabolism to the nervous system: Virtually all processes in health and disease rely on the careful orchestration of a large number of diverse individual components ranging from molecules to cells ... ...

Abstract	From protein interactions to signal transduction, from metabolism to the nervous system: Virtually all processes in health and disease rely on the careful orchestration of a large number of diverse individual components ranging from molecules to cells and entire organs. Networks provide a powerful framework for describing and understanding these complex systems in a wholistic fashion. They offer a unique combination of a highly intuitive, qualitative description, and a plethora of analytical, quantitative tools. Here we provide a brief introduction to the emerging field of network medicine. After an overview of the core concepts for connecting network characteristics to biological functions, we review commonly used networks, ranging from the molecular interaction networks that form the basis of all biological processes in the cell to the global transportation networks that govern the spread of global epidemics. Lastly, we highlight current conceptual and practical challenges.
Keywords	covid19
Publisher	Elsevier; PMC
Document type	Article ; Online
DOI	10.1016/b978-0-12-801238-3.11640-x
Database	COVID19

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Article: A versatile information retrieval framework for evaluating profile strength and similarity.

Kalinin, Alexandr A / Arevalo, John / Vulliard, Loan / Serrano, Erik / Tsang, Hillary / Bornholdt, Michael / Rajwa, Bartek / Carpenter, Anne E / Way, Gregory P / Singh, Shantanu

bioRxiv : the preprint server for biology

2024

Abstract: In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging ... ...

Abstract	In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging to evaluate the phenotypic activity of a sample and the phenotypic consistency among samples, due to profiles' high dimensionality, heterogeneous nature, and non-linear properties. Existing methods leave researchers uncertain where to draw boundaries between meaningful biological response and technical noise. Here, we developed a statistical framework that uses the well-established mean average precision (mAP) as a single, data-driven metric to bridge this gap. We validated the mAP framework against established metrics through simulations and real-world data applications, revealing its ability to capture subtle and meaningful biological differences in cell state. Specifically, we used mAP to assess both phenotypic activity for a given perturbation (or a sample) as well as consistency within groups of perturbations (or samples) across diverse high-dimensional datasets. We evaluated the framework on different profile types (image, protein, and mRNA profiles), perturbation types (CRISPR gene editing, gene overexpression, and small molecules), and profile resolutions (single-cell and bulk). Our open-source software allows this framework to be applied to identify interesting biological phenomena and promising therapeutics from large-scale profiling data.
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.01.587631
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Morphological profiling of human T and NK lymphocytes by high-content cell imaging.

German, Yolla / Vulliard, Loan / Kamnev, Anton / Pfajfer, Laurène / Huemer, Jakob / Mautner, Anna-Katharina / Rubio, Aude / Kalinichenko, Artem / Boztug, Kaan / Ferrand, Audrey / Menche, Jörg / Dupré, Loïc

Cell reports

2021 Volume 36, Issue 1, Page(s) 109318

Abstract: The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate ... ...

Abstract	The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate the applicability of high-content imaging to human T and natural killer (NK) cells and develop a pipeline for unbiased analysis of high-definition morphological profiles. Our approach reveals how distinct facets of actin cytoskeleton remodeling shape immunological synapse architecture and affect lytic granule positioning. Morphological profiling of CD8
MeSH term(s)	Actin-Related Protein 2-3 Complex/deficiency ; Actin-Related Protein 2-3 Complex/metabolism ; Adolescent ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/drug effects ; Cell Line ; Cell Shape/drug effects ; Cytoskeleton/drug effects ; Cytoskeleton/metabolism ; Exocytosis/drug effects ; Humans ; Imaging, Three-Dimensional ; Immunological Synapses/drug effects ; Immunological Synapses/metabolism ; Killer Cells, Natural/cytology ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/metabolism ; Male ; Organoselenium Compounds/pharmacology ; Organosilicon Compounds/pharmacology ; Single-Cell Analysis ; T-Lymphocytes/cytology ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism ; Thiones/pharmacology ; Uracil/analogs & derivatives ; Uracil/pharmacology ; Wiskott-Aldrich Syndrome Protein/deficiency ; Wiskott-Aldrich Syndrome Protein/metabolism
Chemical Substances	ARPC1B protein, human ; Actin-Related Protein 2-3 Complex ; CK-869 ; Organoselenium Compounds ; Organosilicon Compounds ; SMIFH2 compound ; Thiones ; Wiskott-Aldrich Syndrome Protein ; Uracil (56HH86ZVCT)
Language	English
Publishing date	2021-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109318
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: BioProfiling.jl: profiling biological perturbations with high-content imaging in single cells and heterogeneous populations.

Vulliard, Loan / Hancock, Joel / Kamnev, Anton / Fell, Christopher W / Ferreira da Silva, Joana / Loizou, Joanna I / Nagy, Vanja / Dupré, Loïc / Menche, Jörg

Bioinformatics (Oxford, England)

2021 Volume 38, Issue 6, Page(s) 1692–1699

Abstract: Motivation: High-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating raw cellular measurements ... ...

Abstract	Motivation: High-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating raw cellular measurements into morphological profiles suitable for testing biological hypotheses. Despite being a critical step, general-purpose and adaptable tools for morphological profiling are lacking and no solution is available for the high-performance Julia programming language. Results: Here, we introduce BioProfiling.jl, an efficient end-to-end solution for compiling and filtering informative morphological profiles in Julia. The package contains all the necessary data structures to curate morphological measurements and helper functions to transform, normalize and visualize profiles. Robust statistical distances and permutation tests enable quantification of the significance of the observed changes despite the high fraction of outliers inherent to high-content screens. This package also simplifies visual artifact diagnostics, thus streamlining a bottleneck of morphological analyses. We showcase the features of the package by analyzing a chemical imaging screen, in which the morphological profiles prove to be informative about the compounds' mechanisms of action and can be conveniently integrated with the network localization of molecular targets. Availability and implementation: The Julia package is available on GitHub: https://github.com/menchelab/BioProfiling.jl. We also provide Jupyter notebooks reproducing our analyses: https://github.com/menchelab/BioProfilingNotebooks. The data underlying this article are available from FigShare, at https://doi.org/10.6084/m9.figshare.14784678.v2. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Software ; Programming Languages ; Microscopy
Language	English
Publishing date	2021-12-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btab853
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Article ; Online: Assessment of community efforts to advance network-based prediction of protein-protein interactions.

Wang, Xu-Wen / Madeddu, Lorenzo / Spirohn, Kerstin / Martini, Leonardo / Fazzone, Adriano / Becchetti, Luca / Wytock, Thomas P / Kovács, István A / Balogh, Olivér M / Benczik, Bettina / Pétervári, Mátyás / Ágg, Bence / Ferdinandy, Péter / Vulliard, Loan / Menche, Jörg / Colonnese, Stefania / Petti, Manuela / Scarano, Gaetano / Cuomo, Francesca /

Hao, Tong / Laval, Florent / Willems, Luc / Twizere, Jean-Claude / Vidal, Marc / Calderwood, Michael A / Petrillo, Enrico / Barabási, Albert-László / Silverman, Edwin K / Loscalzo, Joseph / Velardi, Paola / Liu, Yang-Yu

Nature communications

2023 Volume 14, Issue 1, Page(s) 1582

Abstract: Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental ... ...

Abstract	Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain unmapped. Computational approaches, especially network-based methods, can facilitate the identification of previously uncharacterized PPIs. Many such methods have been proposed. Yet, a systematic evaluation of existing network-based methods in predicting PPIs is still lacking. Here, we report community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict PPIs across six different interactomes of four different organisms: A. thaliana, C. elegans, S. cerevisiae, and H. sapiens. Through extensive computational and experimental validations, we found that advanced similarity-based methods, which leverage the underlying network characteristics of PPIs, show superior performance over other general link prediction methods in the interactomes we considered.
MeSH term(s)	Animals ; Humans ; Protein Interaction Mapping/methods ; Saccharomyces cerevisiae ; Caenorhabditis elegans ; Protein Interaction Maps ; Computational Biology/methods
Language	English
Publishing date	2023-03-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37079-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Assessment of community efforts to advance network-based prediction of protein–protein interactions

Xu-Wen Wang / Lorenzo Madeddu / Kerstin Spirohn / Leonardo Martini / Adriano Fazzone / Luca Becchetti / Thomas P. Wytock / István A. Kovács / Olivér M. Balogh / Bettina Benczik / Mátyás Pétervári / Bence Ágg / Péter Ferdinandy / Loan Vulliard / Jörg Menche / Stefania Colonnese / Manuela Petti / Gaetano Scarano / Francesca Cuomo /

Tong Hao / Florent Laval / Luc Willems / Jean-Claude Twizere / Marc Vidal / Michael A. Calderwood / Enrico Petrillo / Albert-László Barabási / Edwin K. Silverman / Joseph Loscalzo / Paola Velardi / Yang-Yu Liu

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 14

Abstract: Comprehensive understanding of the human protein-protein interaction network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Here the authors summarize the community ... ...

Abstract	Comprehensive understanding of the human protein-protein interaction network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Here the authors summarize the community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict protein-protein interactions.
Keywords	Science ; Q
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.

Schick, Sandra / Rendeiro, André F / Runggatscher, Kathrin / Ringler, Anna / Boidol, Bernd / Hinkel, Melanie / Májek, Peter / Vulliard, Loan / Penz, Thomas / Parapatics, Katja / Schmidl, Christian / Menche, Jörg / Boehmelt, Guido / Petronczki, Mark / Müller, André C / Bock, Christoph / Kubicek, Stefan

Nature genetics

2019 Volume 51, Issue 9, Page(s) 1399–1410

Abstract: Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer ... ...

Abstract	Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer-type-specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knockout cell lines deficient for 22 BAF subunits. We observe strong, specific and sometimes discordant alterations dependent on the targeted subunit and show that these explain intracomplex codependencies, including the synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest approaches to therapeutically target BAF-mutant cancers.
MeSH term(s)	Chromatin Assembly and Disassembly/genetics ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptome
Chemical Substances	ARID2 protein, human ; DNA-Binding Proteins ; Nuclear Proteins ; SMARCC1 protein, human ; SMARCC2 protein, human ; Transcription Factors ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2019-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-019-0477-9
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

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Article ; Online: Mutational landscape of the transcriptome offers putative targets for immunotherapy of myeloproliferative neoplasms.

Schischlik, Fiorella / Jäger, Roland / Rosebrock, Felix / Hug, Eva / Schuster, Michael / Holly, Raimund / Fuchs, Elisabeth / Milosevic Feenstra, Jelena D / Bogner, Edith / Gisslinger, Bettina / Schalling, Martin / Rumi, Elisa / Pietra, Daniela / Fischer, Gottfried / Faé, Ingrid / Vulliard, Loan / Menche, Jörg / Haferlach, Torsten / Meggendorfer, Manja /

Stengel, Anna / Bock, Christoph / Cazzola, Mario / Gisslinger, Heinz / Kralovics, Robert

Blood

2019 Volume 134, Issue 2, Page(s) 199–210

Abstract: Ph-negative myeloproliferative neoplasms (MPNs) are hematological cancers that can be subdivided into entities with distinct clinical features. Somatic mutations ... ...

Abstract	Ph-negative myeloproliferative neoplasms (MPNs) are hematological cancers that can be subdivided into entities with distinct clinical features. Somatic mutations in
MeSH term(s)	Aged ; Antigens, Neoplasm/genetics ; Calreticulin/genetics ; Female ; Humans ; Immunotherapy/methods ; Male ; Middle Aged ; Mutation ; Myeloproliferative Disorders/genetics ; Receptors, Thrombopoietin/genetics ; Sequence Analysis, RNA/methods ; Transcriptome
Chemical Substances	Antigens, Neoplasm ; CALR protein, human ; Calreticulin ; Receptors, Thrombopoietin ; MPL protein, human (143641-95-6)
Language	English
Publishing date	2019-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2019000519
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Article ; Online: Environmental arginine controls multinuclear giant cell metabolism and formation.

Brunner, Julia S / Vulliard, Loan / Hofmann, Melanie / Kieler, Markus / Lercher, Alexander / Vogel, Andrea / Russier, Marion / Brüggenthies, Johanna B / Kerndl, Martina / Saferding, Victoria / Niederreiter, Birgit / Junza, Alexandra / Frauenstein, Annika / Scholtysek, Carina / Mikami, Yohei / Klavins, Kristaps / Krönke, Gerhard / Bergthaler, Andreas / O'Shea, John J /

Weichhart, Thomas / Meissner, Felix / Smolen, Josef S / Cheng, Paul / Yanes, Oscar / Menche, Jörg / Murray, Peter J / Sharif, Omar / Blüml, Stephan / Schabbauer, Gernot

Nature communications

2020 Volume 11, Issue 1, Page(s) 431

Abstract: Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor ... ...

Abstract	Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome in multiple murine arthritis models and its removal induces preosteoclast metabolic quiescence, associated with impaired tricarboxylic acid (TCA) cycle function and metabolite induction. Effects of arginine deprivation on osteoclastogenesis are independent of mTORC1 activity or global transcriptional and translational inhibition. Arginine scarcity also dampens generation of IL-4 induced MGCs. Strikingly, in extracellular arginine absence, both cell types display flexibility as their formation can be restored with select arginine precursors. These data establish how environmental amino acids control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodelling.
MeSH term(s)	Animals ; Arginine/metabolism ; Arthritis/genetics ; Arthritis/metabolism ; Arthritis/physiopathology ; Bone Remodeling ; Citric Acid Cycle ; Female ; Giant Cells/cytology ; Giant Cells/immunology ; Humans ; Interleukin-4/metabolism ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Mice, Inbred C57BL ; Osteoclasts/cytology ; Osteoclasts/metabolism ; Osteogenesis ; RANK Ligand/genetics ; RANK Ligand/metabolism
Chemical Substances	RANK Ligand ; Interleukin-4 (207137-56-2) ; Arginine (94ZLA3W45F) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2020-01-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-14285-1
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Article ; Online: Environmental arginine controls multinuclear giant cell metabolism and formation

Julia S. Brunner / Loan Vulliard / Melanie Hofmann / Markus Kieler / Alexander Lercher / Andrea Vogel / Marion Russier / Johanna B. Brüggenthies / Martina Kerndl / Victoria Saferding / Birgit Niederreiter / Alexandra Junza / Annika Frauenstein / Carina Scholtysek / Yohei Mikami / Kristaps Klavins / Gerhard Krönke / Andreas Bergthaler / John J. O’Shea /

Thomas Weichhart / Felix Meissner / Josef S. Smolen / Paul Cheng / Oscar Yanes / Jörg Menche / Peter J. Murray / Omar Sharif / Stephan Blüml / Gernot Schabbauer

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 15

Abstract: Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact ... ...

Abstract	Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.
Keywords	Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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