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      A generative network model of neurodevelopmental diversity in structural brain organization

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          Abstract

          The formation of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms drive diversity in organization? We use generative network modeling to provide a computational framework for understanding neurodevelopmental diversity. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over time. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity in neurodevelopment, capable of integrating different levels of analysis—from genes to cognition.

          Abstract

          The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

            In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.
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              The UK Biobank resource with deep phenotyping and genomic data

              The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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                Author and article information

                Contributors
                danyal.akarca@mrc-cbu.cam.ac.uk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                9 July 2021
                9 July 2021
                2021
                : 12
                : 4216
                Affiliations
                [1 ]GRID grid.5335.0, ISNI 0000000121885934, MRC Cognition and Brain Sciences Unit, , University of Cambridge, ; Cambridge, UK
                [2 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Psychiatry, , University of Cambridge, ; Cambridge, UK
                [3 ]GRID grid.499548.d, ISNI 0000 0004 5903 3632, The Alan Turing Institute, ; London, UK
                [4 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, , University of Cambridge, ; Cambridge, UK
                Author information
                http://orcid.org/0000-0002-5931-0295
                http://orcid.org/0000-0002-8955-8283
                Article
                24430
                10.1038/s41467-021-24430-z
                8270998
                34244490
                52614c52-5eac-40c6-a5d9-ce6ee94887e6
                © Crown 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 November 2020
                : 27 May 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);
                Funded by: FundRef https://doi.org/10.13039/100000913, James S. McDonnell Foundation (McDonnell Foundation);
                Funded by: FundRef https://doi.org/10.13039/501100003343, Cambridge Commonwealth, European and International Trust (Cambridge Commonwealth, European & International Trust);
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                network models,neuronal development,dynamic networks,neurodevelopmental disorders

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