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The current coronavirus disease of 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions can provide fine-grained resolution of the mechanisms behind the virus biology and the human organism response. We present a curated dataset of physical molecular interactions focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family that has been manually extracted by International Molecular Exchange (IMEx) Consortium curators. Currently, the dataset comprises over 4400 binarized interactions extracted from 151 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (https://www.ebi.ac.uk/intact) and will be continuously updated as research on COVID-19 progresses. [ABSTRACT FROM AUTHOR]

Background: Lichen planus (LP) is a chronic mucocutaneous inflammatory disease with significant morbidity but data on epidemiology and therapeutics for LP is limited., Objective: To describe overall prevalence of LP and dermatologist-prescribed LP treatments in US adults., Methods: Using the Explorys database, we analyzed prevalence of overall LP and dermatologists' utilization of medications of interest., Results: Among 566,851 eligible patients in the prevalence analysis, there were 1098 LP cases with a median age of 66 years. Overall crude prevalence of LP was 0.19% (95% CI 0.18-0.21) with higher prevalence in females (prevalence ratio vs males 1.77, 95% CI 1.53-2.05). Standardized overall prevalence was 0.15%. Most LP patients diagnosed by dermatologists remained untreated after 1 year (n = 1061, 53%); the most common initial treatment was topical corticosteroids (38%). Treatment continuation after 1 year and switching were most common after initial use of systemic immunosuppressants (28% and 46%, respectively)., Limitations: The lack of a precise diagnosis code for nonoral LP allows for the potential of misclassification; disease severity cannot be established., Conclusions and Relevance: Standardized prevalence of overall LP was 0.15%. For patients requiring systemic immunosuppressive medications, treatment continuation and switching were more common, suggesting that further research into medication selection for LP may be clinically beneficial., Competing Interests: Conflicts of interest Dr Toro and Author Strunk have no conflicts of interest to declare. Dr Garg is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB, Union Therapeutics, Ventyx Biosciences, and Viela Biosciences, and receives honoraria. He receives research grants from AbbVie, UCB, National Psoriasis Foundation, and CHORD COUSIN Collaboration (C3). He is also a cocopyright holder of the HS-IGA and HiSQOL instruments. Dr Han reports honoraria or research grants from AbbVie, Amgen, Arcutis, Athenex, Bausch Health, Boehringer Ingelheim, Bond Avillion, Bristol Myers Squibb, Celgene Corporation, Dermavant, DermTech, Eli Lilly and Company, EPI Health, Janssen Pharmaceuticals, LEO Pharma, MC2 Therapeutics, Novartis, Ortho Dermatologics, PellePharm, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, SUN Pharmaceutical Industries Ltd, and UCB., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The International Molecular Exchange Consortium (IMEx) has evolved into a vital partnership of open resources dedicated to curating molecular interaction data from the scientific literature. This consortium, which includes IntAct, MINT, MatrixDB, and DIP, is a collaborative effort with a central mission of aggregating detailed molecular interaction experimental evidence in a machine-readable format, supported by controlled vocabularies and standard ontologies. The IntAct molecular interaction database (www.ebi.ac.uk/intact), as an IMEx partner, serves as a valuable portal for accessing IMEx data through user-friendly search options and an array of interactive filters. The resource currently hosts an extensive repository of 1,293,508 binary interactions meticulously captured from 75,098 experiments documented in 23,366 publications (as of the February 2024 release), with this corpora being added to by regular data releases. IMEx curation policy has consistently prioritized a fine-grained data and curation model, with a focus on capturing the relevant experimental details essential for interpreting molecular interaction data effectively. Our curation process is designed to support the generation of interactomes tailored to contexts such as disease-specific or tissue-/cell-type-specific interactomes. These interactions are ranked according to a scoring system based on the Proteomics Standard Initiative Molecular Interaction (PSI MI) standards. This scoring system allows users to assess the degree of confidence in binary interactions, enhancing the value of the data. The resource provides insights into the nature of relationships among interacting partners as defined by the experimental setup and the associated biological context. Interactive filters enable users to navigate these rich, multilayered data, promoting a deeper understanding of biological complexity. Additionally, the IntAct website fosters the creation of networks for collaborative analyses by the scientific community. The recent transformation of the IntAct website, supported by a graph-type database, empowers users to execute custom queries tailored to their specific research interests. This article illustrates the diverse levels of annotations available for interactions and the multiple search options at users' disposal to access data of interest. © 2024 European Molecular Biology Laboratory, European Bioinformatics Institute. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Using Quick Search, network visualization, and filters Support Protocol: Accessing fine annotations from intact: Unlocking the molecular details Alternate Protocol: Using batch search: Querying multiple interactors Basic Protocol 2: Using advanced search: Precision and customization., (© 2024 European Molecular Biology Laboratory, European Bioinformatics Institute. Current Protocols published by Wiley Periodicals LLC.)

Importance: Lichen planopilaris (LPP) is a form of scarring alopecia associated with progressive, permanent hair loss. Symptoms range from burning pain to itching, also carrying substantial psychological morbidity. Yet, disease characteristics, pathophysiology, and effective treatment data are limited, making treatment a challenge., Objective: To describe the prevalence and dermatologist-prescribed treatment patterns of LPP among US adults., Design, Setting, and Participants: This cross-sectional study used the Explorys database. The prevalence analysis used a 15% random sample and identified US adults with LPP diagnoses between 2017 and 2019. The LPP treatment analysis included all patients with LPP diagnoses between 2016 and 2020 and a dermatologist encounter in the first year after diagnosis. Data were analyzed from January 2023 to April 2023., Main Outcomes and Measures: The main outcomes of the prevalence analysis were the crude and standardized prevalence estimates of US adults with LPP across age, sex, and racial groups. The main outcomes of the treatment analysis were the frequency of LPP treatments within 1 year of diagnosis, and the number of patients who continued treatment beyond 1 year, switched treatments, and combined treatments., Results: Among 1 466 832 eligible patients analyzed for prevalence, 241 patients had an LPP diagnosis (222 [92.1%] female; median [IQR] age, 64 [54-73] years). Standardized overall prevalence was 13.4 per 100 000 (95% CI, 11.7-15.1). In the treatment analysis, 991 patients had an LPP diagnosis (907 [91.5%] female; median (IQR) age, 60 [47-69] years). Most received at least 1 type of medication (635 [64.1%]), most frequently intralesional corticosteroids (370 [37.3%]) and topical corticosteroids (342 [34.5%]), followed by doxycycline (104 [10.5%]) and hydroxychloroquine (72 [7.3%]). Treatment continued beyond 1 year in 71 of 200 patients (35.5%) prescribed intralesional corticosteroids and 7 of 29 patients (24.1%) prescribed hydroxychloroquine. Treatment switching at 1 year occurred in 32 of 254 patients (12.6%) first prescribed an intralesional corticosteroid and in 44 of 194 (22.7%) first prescribed a topical corticosteroid. Combinations of 2 or 3 treatment types were given to 137 (13.8%) and 74 (7.5%) patients, respectively., Conclusions and Relevance: This cross-sectional study reported prevalence and treatment patterns for US adults with LPP in a representative sample. Most patients with LPP received treatment, and many received multiple treatment types and switched treatments, suggesting further research into medication selection offers clinical benefit.

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit., Competing Interests: Steve R. Feldman received compensation from AbbVie, Accordant, Advance Medical, Almirall, Alovtech, Amgen, Arcutis, Arena, Argenx, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Caremark, Celgene, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline/Stiefel, Helsinn, Informa, Janssen, Leo Pharma, Menlo, Merck, Mylan, National Biological Corporation, National Psoriasis Foundation Novan, Novartis, Pfizer, Qurient Forte, Regeneron, Samsung, Sanofi, Sun Pharma, Suncare Research, UCB, UpToDate, Valeant, and vTv Therapeutics and is the founder and majority owner of www.DrScore.com and the founder and part owner of Causa Research. Abby Van Voorhees is consultant for Novartis, Celgene, Novartis, Merck, Dermira, UCB, BMS, Amgen, and Boehringer Ingelheim and conducts research for AbbVie, Novartis, and Allergan. Lawrence Green is investigator, speaker, and/or consultant for AbbVie, Amgen Inc, Arcutis, Dermavant, MC2, Novartis, Lilly, OrthoDerm, SunPharma, and UCB. Sergio Schwartzman has received consulting fees, research grants, speakers’ bureau activity, or ownership or partnership from 10.13039/100006483AbbVie, 10.13039/100002429Amgen, Boston Scientifc, Crescendo Bioscience, Dermtech, Eli Lilly, 10.13039/100004328Genentech, 10.13039/100005564Gilead Sciences, Janssen, 10.13039/100004374Medtronic, Myriad Genetics, 10.13039/100003185National Psoriasis Foundation, 10.13039/100004336Novartis, Pfzer, 10.13039/100009857Regeneron, 10.13039/100004358Samsung, Sanof, and UCB and has participated in the advisory boards of Jubilant, Myriad, and Stelexis. Evan Siegel has received research grants, consulting fees, and speaker fees from 10.13039/100006483AbbVie, BMS, Eli Lilly, 10.13039/100004336Novartis, Janssen, and UCB. Kelly M. Cordoro is a founding member of the Psoriasis Investigator Group of the Pediatric Dermatology Research Alliance, a counselor for the International Psoriasis Council, and contributor of psoriasis educational materials to the American Academy of Dermatology. Leon Kircik has received research grants from 10.13039/100006483AbbVie, 10.13039/100007819Allergan, Almirall, 10.13039/100002429Amgen, Arcutis, 10.13039/100001003Boehringer Ingelheim, Breckinridge Pharma, Bristol Myers Squibb, 10.13039/100006436Celgene, Cellceutix, Centocor, Combinatrix, Connetics, Coria, Dermavant, 10.13039/100013988Dermira, Dow Pharma, Dr Reddy’s Laboratories, Eli Lilly, 10.13039/501100009754Galderma, 10.13039/100004328Genentech, 10.13039/100004330GlaxoSmithKline, Idera, 10.13039/100004331Johnson & Johnson, Leo Pharma, Maruho, 10.13039/100004334Merck, Medicis, 10.13039/100004336Novartis AG, 10.13039/100004319Pfizer, PharmaDerm, Promis, Stiefel, 10.13039/501100013671Sun Pharma, UCB, 10.13039/100011284Valeant, and XenoPort and has received honoraria from 10.13039/100006483AbbVie, 10.13039/100007819Allergan, Almirall, 10.13039/100002429Amgen, Arcutis, 10.13039/100006314Biogen Idec, Bristol Myers Squibb, 10.13039/100006436Celgene, Cipher, Connetics, Dermavant, 10.13039/100013988Dermira, Dr Reddy’s Laboratories, Eli Lilly, 10.13039/501100009754Galderma, 10.13039/100004328Genentech, 10.13039/100004330GlaxoSmithKline, 10.13039/100004331Johnson & Johnson, Leo Pharma, 10.13039/100004334Merck, 10.13039/100004336Novartis AG, PharmaDerm, Promis, Serono (10.13039/100004334Merck Serono International SA), Stiefel, 10.13039/501100013671Sun Pharma, Taro, UCB, and 10.13039/100011284Valeant. Wilson Liao has received research grant funding from 10.13039/100006483AbbVie, 10.13039/100002429Amgen, Janssen, Leo, 10.13039/100004336Novartis, 10.13039/100004319Pfizer, 10.13039/100009857Regeneron, and TRex Bio. Jason E. Hawkes has received personal fees/honoraria from 10.13039/100006483AbbVie, Janssen, LearnSkin, LEO Pharma, 10.13039/100004336Novartis, 10.13039/100004319Pfizer, 10.13039/100004339Sanofi, UpToDate, and VisualDx. Jeffrey Weinberg is a speaker for AbbVie, Amgen, Eli Lilly, Novartis, Sun, Leo Pharma, and Pfizer and an investigator for Dermavant, AbbVie, Corrona Psoriasis Registry, Dermira, Lilly, Novartis, and Pfizer. John Koo has served as an advisor for AbbVie, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, EPI, Novartis, Pfizer, Sun Pharma, and Ortho Dermatologics, Regeneron/Sanofi, and UCB. Elizabeth Brezinski Wallace serves as an investigator for Pfizer and Target Real World Evidence. April Armstrong is investigator for Sanofi Genzyme, Bristol Myers Squibb, Dermavant, Dermira, Eli Lily, Galderma, Janssen–Ortho, Inc, Kyowa Hakko Kirin, AbbVie, Janssen Pharmaceuticals Inc, Leo Pharma, Modernizing Medicine, Novartis Pharmaceuticals Corp, Ortho Dermatologics, Pfizer Inc, Regeneron Pharmaceuticals, Sun Pharma, and UCB Pharma; a speaker for AbbVie, Regeneron Pharmaceuticals, and Sanofi Genzyme; and on the data safety monitoring board for Boehringer Ingelheim/ Parexel. George Han is investigator, consultant/advisor, or speaker for AbbVie, Amgen, Arcutis, Athenex, Bausch Health, Boehringer Ingelheim, Bond Avillion, Bristol Myers Squibb, Celgene Corporation, Dermavant, DermTech, Eli Lilly and Company, EPI Health, Janssen Pharmaceuticals, LEO Pharma, MC2 Therapeutics, Novartis, Ortho Dermatologics, PellePharm, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, SUN Pharmaceutical Industries Ltd, and UCB and conducts research for Bausch Health, Eli Lilly and Company, Janssen Pharmaceuticals, and Novartis. Natalia Pelet del Toro, Rayan Yahia, Seemal R. Desai, and Leah M. Howard have no conflicts to declare., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Interacting proteins tend to have similar functions, influencing the same organismal traits. Interaction networks can be used to expand the list of candidate trait-associated genes from genome-wide association studies. Here, we performed network-based expansion of trait-associated genes for 1,002 human traits showing that this recovers known disease genes or drug targets. The similarity of network expansion scores identifies groups of traits likely to share an underlying genetic and biological process. We identified 73 pleiotropic gene modules linked to multiple traits, enriched in genes involved in processes such as protein ubiquitination and RNA processing. In contrast to gene deletion studies, pleiotropy as defined here captures specifically multicellular-related processes. We show examples of modules linked to human diseases enriched in genes with known pathogenic variants that can be used to map targets of approved drugs for repurposing. Finally, we illustrate the use of network expansion scores to study genes at inflammatory bowel disease genome-wide association study loci, and implicate inflammatory bowel disease-relevant genes with strong functional and genetic support., (© 2023. The Author(s).)

Background: Case identification strategies to conduct population-based studies have not been developed for lichen planus (LP) or lichen planopilaris (LPP)., Objectives: The aim of this study was to assess the validity of using diagnostic codes to establish both a cutaneous (non-oral) LP cohort and an LPP cohort from a large clinical database., Methods: A retrospective chart review was performed to determine whether patients with ICD-9 or ICD-10 codes for LP and ICD-10 codes for LPP are confirmed cases of LP and LPP. Validation samples were used to estimate the positive predictive value (PPV) of three case definitions any LP, non-oral LP, and LPP defined as: at least one code by any physician, at least two codes by any physician, and at least one code by a dermatologist., Results: Among the 199 reviewed LP charts, 166 and 123 were confirmed cases of any LP and non-oral LP, respectively. The PPVs for any LP were: 83.4% (166/199) for one code by any physician, 84.6% (77/91) for two codes by any physician, and 95.1% (97/102) for one code by a dermatologist. The PPVs for non-oral LP were: 61.8% (123/199) for one code by any physician, 70.3% (64/91) for two diagnoses by any physician, and 86.3% (88/102) for one diagnosis by a dermatologist. Of the 139 patients with at least one code for LPP, 122 were confirmed cases of LPP. The case definition for one LPP code applied by any physician had a PPV of 87.8% (122/139) to identify a true case of LPP, whereas two diagnoses by any physician had a PPV of 96.2% (76/79) and a diagnosis by a dermatologist had a PPV of 93% (107/115)., Conclusions: Diagnosis codes for LP and LPP, restricted by the diagnosing physician's specialty, may be used to accurately identify case cohorts of overall LP, non-oral LP, or LPP in large clinical databases., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated, encyclopaedic database of macromolecular complexes with known function from a range of model organisms. It summarizes complex composition, topology and function along with links to a large range of domain-specific resources (i.e. wwPDB, EMDB and Reactome). Since the last update in 2019, we have produced a first draft complexome for Escherichia coli, maintained and updated that of Saccharomyces cerevisiae, added over 40 coronavirus complexes and increased the human complexome to over 1100 complexes that include approximately 200 complexes that act as targets for viral proteins or are part of the immune system. The display of protein features in ComplexViewer has been improved and the participant table is now colour-coordinated with the nodes in ComplexViewer. Community collaboration has expanded, for example by contributing to an analysis of putative transcription cofactors and providing data accessible to semantic web tools through Wikidata which is now populated with manually curated Complex Portal content through a new bot. Our data license is now CC0 to encourage data reuse. Users are encouraged to get in touch, provide us with feedback and send curation requests through the 'Support' link., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The IntAct molecular interaction database (https://www.ebi.ac.uk/intact) is a curated resource of molecular interactions, derived from the scientific literature and from direct data depositions. As of August 2021, IntAct provides more than one million binary interactions, curated by twelve global partners of the International Molecular Exchange consortium, for which the IntAct database provides a shared curation and dissemination platform. The IMEx curation policy has always emphasised a fine-grained data and curation model, aiming to capture the relevant experimental detail essential for the interpretation of the provided molecular interaction data. Here, we present recent curation focus and progress, as well as a completely redeveloped website which presents IntAct data in a much more user-friendly and detailed way., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The origin and evolution of cancer cells is considered to be mainly fueled by DNA mutations. Although translation errors could also expand the cellular proteome, their role in cancer biology remains poorly understood. Tumor suppressors called caretakers block cancer initiation and progression by preventing DNA mutations and/or stimulating DNA repair. If translational errors contribute to tumorigenesis, then caretaker genes should prevent such errors in normal cells in response to oncogenic stimuli. Here, we show that the process of cellular senescence induced by oncogenes, tumor suppressors or chemotherapeutic drugs is associated with a reduction in translational readthrough (TR) measured using reporters containing termination codons withing the context of both normal translation termination or programmed TR. Senescence reduced both basal TR and TR stimulated by aminoglycosides. Mechanistically, the reduction of TR during senescence is controlled by the RB tumor suppressor pathway. Cells that escape from cellular senescence either induced by oncogenes or chemotherapy have an increased TR. Also, breast cancer cells that escape from therapy-induced senescence express high levels of AGO1x, a TR isoform of AGO1 linked to breast cancer progression. We propose that senescence and the RB pathway reduce TR limiting proteome diversity and the expression of TR proteins required for cancer cell proliferation., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Summary: IntAct App is a Cytoscape 3 application that grants in-depth access to IntAct's molecular interaction data. It build networks where nodes are interacting molecules (mainly proteins, but also genes, RNA, chemicals…) and edges represent evidence of interaction. Users can query a network by providing its molecules, identified by different fields and optionally include all their interacting partners in the resulting network. The app offers three visualizations: one only displaying interactions, another representing every evidence and the last one emphasizing evidence where mutated versions of proteins were used. Users can also filter networks and click on nodes and edges to access all their related details. Finally, the application supports automation of its main features via Cytoscape commands., Availability and Implementation: Implementation available at https://apps.cytoscape.org/apps/intactapp, while the source code is available at https://github.com/EBI-IntAct/IntactApp., (© The Author(s) 2021. Published by Oxford University Press.)

The electroencephalographic signal constitutes the main sign classically used for the identification of states of alertness. However, activities in the high frequency (>100 Hz) range have not been properly studied despite their high potential for sleep scoring in rodents. In the present study, we designed a method for the identification of the sleep-wake states in rats by exclusively using high-frequency activities of the electroencephalogram. By calculating the ratio between the amplitude of the electroencephalographic signal from 110 to 200 Hz and from 110 to 300 Hz, we obtained an index that had values that were low during wakefulness, intermediate during non-REM sleep and high during REM sleep. This high-frequency index (HiFI) allowed the identification of each state without the need to study other signs such as muscle activity or eye movements. To evaluate the performance of the index, we compared it with the conventional scoring of the sleep-wake cycle based upon the study of the electromyogram and delta (0.5-4 Hz), theta (6-9 Hz) and sigma (10-14 Hz) bands of the electroencephalogram. The index had an accuracy of 90.43 ± 1.91% (Cohen's kappa value of 0.82), confirming that the study of the high-frequency activities of the electroencephalogram was sufficient to reliably identify alertness states in the rat. Compared to other sleep-scoring methods, the HiFI has several advantages. It only requires one electroencephalography electrode, thus reducing the severity of the surgical preparation of the experimental animal, and its calculation is very simple, so it can be easily implemented online to classify sleep-wake states in real time., (© 2020 European Sleep Research Society.)

The EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data are freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration with Saccharomyces Genome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organism Saccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are more multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Motivation: A large variety of molecular interactions occurs between biomolecular components in cells. When a molecular interaction results in a regulatory effect, exerted by one component onto a downstream component, a so-called 'causal interaction' takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g. gene regulation) need to be described with a careful appreciation of the underlying molecular reactions. A proper description of this information enables archiving, sharing and reuse by humans and for automated computational processing. Various representations of causal relationships between biological components are currently used in a variety of resources., Results: Here, we propose a checklist that accommodates current representations, called the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while fostering uniformity and interoperability of the data across resources., Availability and Implementation: The checklist together with examples is accessible at https://github.com/MI2CAST/MI2CAST., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press.)

The International Molecular Exchange (IMEx) Consortium provides scientists with a single body of experimentally verified protein interactions curated in rich contextual detail to an internationally agreed standard. In this update to the work of the IMEx Consortium, we discuss how this initiative has been working in practice, how it has ensured database sustainability, and how it is meeting emerging annotation challenges through the introduction of new interactor types and data formats. Additionally, we provide examples of how IMEx data are being used by biomedical researchers and integrated in other bioinformatic tools and resources.

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website ( www.ebi.ac.uk/intact ), and will be continuously updated as research on COVID-19 progresses.

Senescence is a tumor suppressor program characterized by a stable growth arrest while maintaining cell viability. Senescence-associated ribogenesis defects (SARD) have been shown to regulate senescence through the ability of the ribosomal protein S14 (RPS14 or uS11) to bind and inhibit the cyclin-dependent kinase 4 (CDK4). Here we report another ribosomal protein that binds and inhibits CDK4 in senescent cells: L22 (RPL22 or eL22). Enforcing the expression of RPL22/eL22 is sufficient to induce an RB and p53-dependent cellular senescent phenotype in human fibroblasts. Mechanistically, RPL22/eL22 can interact with and inhibit CDK4-Cyclin D1 to decrease RB phosphorylation both in vitro and in cells. Briefly, we show that ribosome-free RPL22/eL22 causes a cell cycle arrest which could be relevant during situations of nucleolar stress such as cellular senescence or the response to cancer chemotherapy.

The Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated, encyclopaedic database that collates and summarizes information on stable, macromolecular complexes of known function. It captures complex composition, topology and function and links out to a large range of domain-specific resources that hold more detailed data, such as PDB or Reactome. We have made several significant improvements since our last update, including improving compliance to the FAIR data principles by providing complex-specific, stable identifiers that include versioning. Protein complexes are now available from 20 species for download in standards-compliant formats such as PSI-XML, MI-JSON and ComplexTAB or can be accessed via an improved REST API. A component-based JS front-end framework has been implemented to drive a new website and this has allowed the use of APIs from linked services to import and visualize information such as the 3D structure of protein complexes, its role in reactions and pathways and the co-expression of complex components in the tissues of multi-cellular organisms. A first draft of the complete complexome of Saccharomyces cerevisiae is now available to browse and download.

Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence. Genetic analysis revealed that Rb but not p53 was required for the senescence response to altered ribosome biogenesis. Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the soluble non-ribosomal fraction of senescent cells, where it binds and inhibits CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we describe a mechanism for maintaining the senescent cell cycle arrest that may be relevant for cancer therapy, as well as biomarkers to identify senescent cells.

The current catalogue of the human proteome is not yet complete, as experimental proteomics evidence is still elusive for a group of proteins known as the missing proteins. The Human Proteome Project (HPP) has been successfully using technology and bioinformatic resources to improve the characterization of such challenging proteins. In this manuscript, we propose a pipeline starting with the mining of the PRIDE database to select a group of data sets potentially enriched in missing proteins that are subsequently analyzed for protein identification with a method based on the statistical analysis of proteotypic peptides. Spermatozoa and the HEK293 cell line were found to be a promising source of missing proteins and clearly merit further attention in future studies. After the analysis of the selected samples, we found 342 PSMs, suggesting the presence of 97 missing proteins in human spermatozoa or the HEK293 cell line, while only 36 missing proteins were potentially detected in the retina, frontal cortex, aorta thoracica, or placenta. The functional analysis of the missing proteins detected confirmed their tissue specificity, and the validation of a selected set of peptides using targeted proteomics (SRM/MRM assays) further supports the utility of the proposed pipeline. As illustrative examples, DNAH3 and TEPP in spermatozoa, and UNCX and ATAD3C in HEK293 cells were some of the more robust and remarkable identifications in this study. We provide evidence indicating the relevance to carefully analyze the ever-increasing MS/MS data available from PRIDE and other repositories as sources for missing proteins detection in specific biological matrices as revealed for HEK293 cells.

Mass spectrometry (MS) is the main technology used in proteomics approaches. However, on average 75% of spectra analysed in an MS experiment remain unidentified. We propose to use spectrum clustering at a large-scale to shed a light on these unidentified spectra. PRoteomics IDEntifications database (PRIDE) Archive is one of the largest MS proteomics public data repositories worldwide. By clustering all tandem MS spectra publicly available in PRIDE Archive, coming from hundreds of datasets, we were able to consistently characterize three distinct groups of spectra: 1) incorrectly identified spectra, 2) spectra correctly identified but below the set scoring threshold, and 3) truly unidentified spectra. Using a multitude of complementary analysis approaches, we were able to identify less than 20% of the consistently unidentified spectra. The complete spectrum clustering results are available through the new version of the PRIDE Cluster resource (http://www.ebi.ac.uk/pride/cluster). This resource is intended, among other aims, to encourage and simplify further investigation into these unidentified spectra., Competing Interests: The authors declare no competing financial interests.