PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive

Enabling FAIR data stewardship in complex international multi-site studies: Data Operations for the Accelerating Medicines Partnership® Schizophrenia Program.

Modern research management, particularly for publicly funded studies, assumes a data governance model in which grantees are considered stewards rather than owners of important data sets. Thus, there is an expectation that collected data are shared as widely as possible with the general research community. This presents problems in complex studies that involve sensitive health information. The latter requires balancing participant privacy with the needs of the research community. Here, we report on the data operation ecosystem crafted for the Accelerating Medicines Partnership® Schizophrenia project, an international observational study of young individuals at clinical high risk for developing a psychotic disorder. We review data capture systems, data dictionaries, organization principles, data flow, security, quality control protocols, data visualization, monitoring, and dissemination through the NIMH Data Archive platform. We focus on the interconnectedness of these steps, where our goal is to design a seamless data flow and an alignment with the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles while balancing local regulatory and ethical considerations. This process-oriented approach leverages automated pipelines for data flow to enhance data quality, speed, and collaboration, underscoring the projects contribution to advancing research practices involving multisite studies of sensitive mental health conditions. An important feature is the datas close-to-real-time quality assessment (QA) and quality control (QC). The focus on close-to-real-time QA/QC makes it possible for a subject to redo a testing session, as well as facilitate course corrections to prevent repeating errors in future data acquisition. Watch Dr. Sylvain Bouix discuss his work and this article: https://vimeo.com/1025555648

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals

PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe – Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive

RATP Fall 2020 Demo Project

“A project to test the relationship between whether or not someone speaks more than one language natively and their willingness to initiate conversations with people outside of their social circle

The effect of language dominance on the expression of emotions and mood symptoms in bilingual (Spanish-English) individuals

Prior research has demonstrated that psychiatric symptoms may be expressed differently across languages in multilingual individuals (Southwood, 2008). This discrepancy was first observed in two sets of case studies (Del Castillo, 1970; Hemphill, 1971) published over fifty years ago that indicate that seriously mentally ill patients (e.g., those with schizophrenia or bipolar disorder) appear to display more severe psychopathology when assessed in their dominant language. Using a two-sample study, Brown and Weisman de Mamani (2017) confirmed that people with psychosis report greater psychosis symptomology (i.e., thought disturbances) when interviewed in their dominant language. This pattern also held for normative populations when looking at subclinical forms of psychosis, such as unusual experiences and cognitive disorganization. To our knowledge, research has yet to examine whether the manifestation of greater psychopathology in the dominant language also occurs in more common mood symptoms and emotional states, such as depression, sadness or anxiety. Del Castillo (1970) further hypothesized that the effortful control and working memory demands involved in speaking a second language may serve to focus an individual and consequently appease emotions. In the case of individuals with psychosis, this effortful control may put them in closer contact with reality. However, as far as we are aware, Del Castillo’s effortful control hypothesis has never before been tested. The primary objective of this study is to examine whether the pattern of greater observed psychopathology in the dominant language found by prior researchers will extend to more common distressing mood symptoms and emotional states. If hypotheses are supported, it is also important to identify why this pattern occurs. Thus, the second objective of this study is to evaluate whether any differences in emotional distress observed in dominant versus non dominant language are mediated (either fully or partially) by effortful control. By exploring these objectives, this study aims to enhance our understanding of the linguistic nuances in the expression of psychopathology and emotional distress, potentially informing more effective clinical practices for multilingual individuals

Acute (R,S)-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice

(R,S)-ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that was originally developed as an anesthetic. Most recently, (R,S)-ketamine has been used as a rapid-acting antidepressant, and we have reported that (R,S)-ketamine can also be a prophylactic against stress in adult mice. However, most pre-clinical studies have been performed in adult mice. It is still unknown how an acute (R,S)-ketamine injection influences behavior across the lifespan (e.g., to adolescent or aged populations). Here, we administered saline or (R,S)-ketamine at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes. One hour later, behavioral despair, avoidance, locomotion, perseverative behavior, or contextual fear discrimination (CFD) was assessed. A separate cohort of mice was sacrificed 1 h following saline or (R,S)-ketamine administration. Brains were processed to quantify the marker of inflammation Cyclooxygenase 2 (Cox-2) expression to determine whether the acute effects of (R,S)-ketamine were partially mediated by changes in brain inflammation. Our findings show that (R,S)-ketamine reduced behavioral despair and perseverative behavior in adolescent female, but not male, mice and facilitated CFD in both sexes at specific doses. (R,S)-ketamine reduced Cox-2 expression specifically in ventral CA3 (vCA3) of male mice. Notably, (R,S)-ketamine was not effective in aged mice. These results underscore the need for sex- and age-specific approaches to test (R,S)-ketamine efficacy across the lifespan.</jats:p

Prophylactic (<i>R,S</i>)-Ketamine Is Effective Against Stress-Induced Behaviors in Adolescent but Not Aged Mice

Abstract Background (R,S)-ketamine, an N-methyl-D-aspartate receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice but have yet to test its efficacy in adolescent or aged populations. Methods Here, we administered saline or (R,S)-ketamine as a prophylactic at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes 1 week before a 3-shock contextual fear-conditioning (CFC) stressor. Following CFC, we assessed behavioral despair, avoidance, perseverative behavior, locomotion, and contextual fear discrimination. To assess whether the prophylactic effect could persist into adulthood, adolescent mice were injected with saline or varying doses of (R,S)-ketamine and administered a 3-shock CFC as a stressor 1 month later. Mice were then re-exposed to the aversive context 5 days later and administered behavioral tests as aforementioned. Brains were also processed to quantify Cyclooxygenase 2 expression as a proxy for inflammation to determine whether the prophylactic effects of (R,S)-ketamine were partially due to changes in brain inflammation. Results Our data indicate that (R,S)-ketamine is prophylactic at sex-specific doses in adolescent but not aged mice. (R,S)-ketamine attenuated learned fear and perseverative behavior in females, reduced behavioral despair in males, and facilitated contextual fear discrimination in both sexes. (R,S)-ketamine reduced Cyclooxygenase 2 expression specifically in ventral Cornu Ammonis region 3 of male mice. Conclusions These findings demonstrate that prophylactic (R,S)-ketamine efficacy is sex, dose, and age dependent and will inform future studies investigating (R,S)-ketamine efficacy across the lifespan. </jats:sec