New system for archiving integrative structures.
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ABSTRACT:
SUBMITTER: Vallat B
PROVIDER: S-EPMC8647179 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Structures of biomolecular systems are increasingly computed by integrative modeling. In this approach, a structural model is constructed by combining information from multiple sources, including varied experimental methods and prior models. In 2019, a Workshop was held as a Biophysical Society Satellite Meeting to assess progress and discuss further requirements for archiving integrative structures. The primary goal of the Workshop was to build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are presented here.
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Project description:Limitations in the applicability, accuracy, and precision of individual structure characterization methods can sometimes be overcome via an integrative modeling approach that relies on information from all available sources, including all available experimental data and prior models. The open-source Integrative Modeling Platform (IMP) is one piece of software that implements all computational aspects of integrative modeling. To maximize the impact of integrative structures, the coordinates should be made publicly available, as is already the case for structures based on X-ray crystallography, NMR spectroscopy, and electron microscopy. Moreover, the associated experimental data and modeling protocols should also be archived, such that the original results can easily be reproduced. Finally, it is essential that the integrative structures are validated as part of their publication and deposition. A number of research groups have already developed software to implement integrative modeling and have generated a number of structures, prompting the formation of an Integrative/Hybrid Methods Task Force. Following the recommendations of this task force, the existing PDBx/mmCIF data representation used for atomic PDB structures has been extended to address the requirements for archiving integrative structural models. This IHM-dictionary adds a flexible model representation, including coarse graining, models in multiple states and/or related by time or other order, and multiple input experimental information sources. A prototype archiving system called PDB-Dev ( https://pdb-dev.wwpdb.org ) has also been created to archive integrative structural models, together with a Python library to facilitate handling of integrative models in PDBx/mmCIF format.
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Project description:Essential processes in biology are carried out by large macromolecular assemblies, whose structures are often difficult to determine by traditional methods. Increasingly, researchers combine measured data and computed information from several complementary methods to obtain "hybrid" or "integrative" structural models of macromolecules and their assemblies. These integrative/hybrid (I/H) models are not archived in the PDB because of the absence of standard data representations and processing mechanisms. Here we present the development of data standards and a prototype system for archiving I/H models. The data standards provide the definitions required for representing I/H models that span multiple spatiotemporal scales and conformational states, as well as spatial restraints derived from different experimental techniques. Based on these data definitions, we have built a prototype system called PDB-Dev, which provides the infrastructure necessary to archive I/H structural models. PDB-Dev is now accepting structures and is open to the community for new submissions.
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Project description:This study describes an automatic technique to accurately determine the maximum head circumference (MHC) measurement from MRI studies within the Picture Archiving and Communications System, and can automatically add this measurement to the final radiology report. Participants were selected through a retrospective chart review of patients referred to the neurosurgery clinic. Forty-nine pediatric patients with ages ranging from 5 months to 11 years were included in the study. We created 14 printed ring structures to mirror the head circumference values at various ages along the x-axis of the Nellhaus chart. The 3D-printed structures were used to create MRI phantoms. Analytical obtainment of circumference values from the 3D objects and phantom images allowed for a fair estimation and correction of errors on the image-based-measuring instrument. Then, standard manual MHC measurements were performed and compared to values obtained from the patients' MRI T1 images using the tuned instrument proposed in this document. A T-test revealed no statistical difference between the manual assessments and the ones obtained by the automation p = 0.357, α = 0.05. This automatic application augments the more error-prone manual MHC measurement, and can add a numerical value to the final radiology report as a standard application.
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Project description:A plant's architecture contributes to its ability to acquire resources and reduce mechanical load. Arabidopsis thaliana is the most common model plant in molecular biology, and there are several mutants and transgenic lines with modified plant architecture regulation, such as lazy1 mutants, which have reversed angles of lateral branches. Although some phenotyping methods have been used in larger agricultural plants, limited suitable methods are available for three-dimensional reconstruction of Arabidopsis, which is smaller and has more uniform surface textures and structures. An inexpensive, easily adopted three-dimensional reconstruction system that can be used for Arabidopsis is needed so that researchers can view and quantify morphological changes over time. We developed a three-dimensional reconstruction system for A. thaliana using the visual volume intersection method, which uses a fixed camera to capture plant images from multiple directions while the plant slowly rotates. We then developed a script to autogenerate stack images from the obtained input movie and visualized the plant architecture by rendering the output stack image using the general bioimage analysis software. We successfully three-dimensionally and time-sequentially scanned wild-type and lazy1 mutant A. thaliana plants and measured the angles of the lateral branches. This non-contact, non-destructive method requires no specialized equipment and is space efficient, inexpensive and easily adopted by Arabidopsis researchers. Consequently, this system will promote three- and four-dimensional phenotyping of this model plant, and it can be used in combination with molecular genetics to further elucidate the molecular mechanisms that regulate Arabidopsis architecture.
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Project description:CryoEM in structural biology is currently served by three public archives-EMDB for 3DEM reconstructions, PDB for models built from 3DEM reconstructions, and EMPIAR for the raw 2D image data used to obtain the 3DEM reconstructions. These archives play a vital role for both the structural community and the wider biological community in making the data accessible so that results may be reused, reassessed, and integrated with other structural and bioinformatics resources. The important role of the archives is underpinned by the fact that many journals mandate the deposition of data to PDB and EMDB on publication. The field is currently undergoing transformative changes where on the one hand high-resolution structures are becoming a routine occurrence while on the other hand electron tomography is enabling the study of macromolecules in the cellular context. Concomitantly the archives are evolving to best serve their stakeholder communities. In this chapter, we describe the current state of the archives, resources available for depositing, accessing, searching, visualizing and validating data, on-going community-wide initiatives and opportunities, and challenges for the future.
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Project description:BackgroundMultiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology.MethodsWe performed multi-level cerebrospinal fluid (CSF) omics in a well-characterized cohort of older adults with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analyzed at single-omic level with correlation and regression approaches. Multi-omics factor analysis was used to integrate all biological levels. Identified analytes were used to construct best predictive models of the presence of AD pathology and of cognitive decline with multifactorial regression analysis. Pathway enrichment analysis identified pathway alterations in AD.ResultsMulti-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD. Further analysis exposed multiple interactions between single 'omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD. Finally, combinations of four molecules improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1).ConclusionsApplying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
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Project description:BackgroundThe advancement of computer information technology would maximize its potential in operating rooms with touchless input devices. A picture archiving and communication system (PACS) was compared with a touchless input device (LMC-GW), relaying to another person to control a mouse through verbal guidance, and directly controlling a mouse.MethodsParticipants (n = 34; mean age, 29.6 years) were prospectively enrolled and given nine scenarios to compare the three methods. Each scenario consisted of eight tasks, which required 6 essential functions of PACS. Time elapsed and measurement values were recorded for objective evaluation, while subjective evaluation was conducted with a questionnaire.ResultsIn all 8 tasks, manipulation using the mouse took significantly less time than the other methods (all p < 0.05). Study selection, panning, zooming, scrolling, distance measuring, and leg length measurement took significantly less time when LMC-GW was used compared to relaying to another person (all p < 0.01), whereas there were no significant differences in time required for measuring the angles and windowing. Although the touchless input device provided higher accessibility and lower contamination risk, it was more difficult to handle than the other input methods (all p < 0.01).ConclusionsThe touchless input device provided superior or equal performance to the method of verbal instruction in the environment of operating room. Surgeons agreed that the device would be helpful for manipulating PACS in operating rooms with less contamination risk and disturbance of workflow. The touchless input device can be an alternative option for direct manipulation of a mouse in operation rooms in the future.
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