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1.
Science ; 367(6482)2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139519

RESUMO

The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.


Assuntos
Atlas como Assunto , Encéfalo/fisiologia , Regulação da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Transcriptoma , Animais , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos/genética , Especificidade da Espécie , Suínos
2.
Nat Neurosci ; 23(3): 456-467, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066983

RESUMO

Mammalian circadian behaviors are orchestrated by the suprachiasmatic nucleus (SCN) in the ventral hypothalamus, but the number of SCN cell types and their functional roles remain unclear. We have used single-cell RNA-sequencing to identify the basic cell types in the mouse SCN and to characterize their circadian and light-induced gene expression patterns. We identified eight major cell types, with each type displaying a specific pattern of circadian gene expression. Five SCN neuronal subtypes, each with specific combinations of markers, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Through a complete three-dimensional reconstruction of the mouse SCN at single-cell resolution, we obtained a standardized SCN atlas containing the spatial distribution of these subtypes and gene expression. Furthermore, we observed heterogeneous circadian gene expression between SCN neuron subtypes. Such a spatiotemporal pattern of gene regulation within the SCN may have an important function in the circadian pacemaker.


Assuntos
Expressão Gênica/fisiologia , Neurônios/fisiologia , Análise de Célula Única , Núcleo Supraquiasmático/fisiologia , Animais , Atlas como Assunto , Ritmo Circadiano/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Expressão Gênica/efeitos da radiação , Regulação da Expressão Gênica/fisiologia , Genômica , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/classificação , Estimulação Luminosa , Núcleo Supraquiasmático/anatomia & histologia , Núcleo Supraquiasmático/citologia
3.
Science ; 367(6480)2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32079746

RESUMO

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.


Assuntos
Atlas como Assunto , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Timo/crescimento & desenvolvimento , Timo/imunologia , Linfócitos T CD8-Positivos/citologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Fibroblastos/citologia , Fibroblastos/imunologia , Humanos , RNA-Seq/métodos , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Célula Única/métodos , Timo/citologia
4.
Med Hist ; 64(1): 116-141, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31933505

RESUMO

In early twentieth-century France, syphilis and its controversial status as a hereditary disease reigned as a chief concern for physicians and public health officials. As syphilis primarily presented visually on the surface of the skin, its study fell within the realms of both dermatologists and venereologists, who relied heavily on visual evidence in their detection, diagnosis, and treatment of the disease. Thus, in educational textbooks, atlases, and medical models, accurately reproducing the visible signposts of syphilis - the colour, texture, and patterns of primary chancres or secondary rashes - was of preeminent importance. Photography, with its potential claims to mechanical objectivity, would seem to provide the logical tool for such representations. Yet photography's relationship to syphilographie warrants further unpacking. Despite the rise of a desire for mechanical objectivity charted in the late nineteenth century, artist-produced, three-dimensional, wax-cast moulages coexisted with photographs as significant educational tools for dermatologists; at times, these models were further mediated through photographic reproduction in texts. Additionally, the rise of phototherapy complicated this relationship by fostering the clinical equation of the light-sensitive photographic plate with the patient's skin, which became the photographic record of disease and successful treatment. This paper explores these complexities to delineate a more nuanced understanding of objectivity vis-à-vis photography and syphilis. Rather than a desire to produce an unbiased image, fin-de-siècle dermatologists marshalled the photographic to exploit the verbal and visual rhetoric of objectivity, authority, and persuasion inextricably linked to culturally constructed understandings of the photograph. This rhetoric was often couched in the Peircean concept of indexicality, which physicians formulated through the language of witness, testimony, and direct connection.


Assuntos
Anatomia Artística/história , Ilustração Médica/história , Modelos Anatômicos , Fotografação/história , Sífilis/história , Atlas como Assunto/história , Distinções e Prêmios , Dermatologia/educação , Dermatologia/história , França , Historiografia , História do Século XIX , História do Século XX , Humanos , Sífilis/patologia , Sífilis Congênita/história , Venereologia/educação , Venereologia/história
6.
Nat Neurosci ; 22(12): 2087-2097, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768052

RESUMO

There is currently little information available about how individual cell types contribute to Alzheimer's disease. Here we applied single-nucleus RNA sequencing to entorhinal cortex samples from control and Alzheimer's disease brains (n = 6 per group), yielding a total of 13,214 high-quality nuclei. We detail cell-type-specific gene expression patterns, unveiling how transcriptional changes in specific cell subpopulations are associated with Alzheimer's disease. We report that the Alzheimer's disease risk gene APOE is specifically repressed in Alzheimer's disease oligodendrocyte progenitor cells and astrocyte subpopulations and upregulated in an Alzheimer's disease-specific microglial subopulation. Integrating transcription factor regulatory modules with Alzheimer's disease risk loci revealed drivers of cell-type-specific state transitions towards Alzheimer's disease. For example, transcription factor EB, a master regulator of lysosomal function, regulates multiple disease genes in a specific Alzheimer's disease astrocyte subpopulation. These results provide insights into the coordinated control of Alzheimer's disease risk genes and their cell-type-specific contribution to disease susceptibility. These results are available at http://adsn.ddnetbio.com.


Assuntos
Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Córtex Entorrinal/metabolismo , Regulação da Expressão Gênica , Predisposição Genética para Doença/genética , Microglia/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Apolipoproteínas E/metabolismo , Atlas como Assunto , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Masculino , Análise de Sequência de RNA , Regulação para Cima
7.
Nat Neurosci ; 22(11): 1903-1912, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31591557

RESUMO

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.


Assuntos
Doença de Alzheimer/metabolismo , Atlas como Assunto , Perfilação da Expressão Gênica , Lobo Parietal/metabolismo , /biossíntese , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Humanos , MicroRNAs/metabolismo , RNA Mensageiro/biossíntese , Análise de Sequência de RNA , Índice de Gravidade de Doença
8.
Nature ; 574(7777): 187-192, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597973

RESUMO

Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions.


Assuntos
Atlas como Assunto , Pesquisa Biomédica/organização & administração , Cooperação Internacional , Modelos Anatômicos , National Institutes of Health (U.S.)/organização & administração , Análise de Célula Única , Envelhecimento , Feminino , Saúde , Humanos , Masculino , Biologia Molecular/organização & administração , Especificidade de Órgãos , Estados Unidos
9.
Nat Neurosci ; 22(11): 1925-1935, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31527803

RESUMO

The thalamus is the central communication hub of the forebrain and provides the cerebral cortex with inputs from sensory organs, subcortical systems and the cortex itself. Multiple thalamic regions send convergent information to each cortical region, but the organizational logic of thalamic projections has remained elusive. Through comprehensive transcriptional analyses of retrogradely labeled thalamic neurons in adult mice, we identify three major profiles of thalamic pathways. These profiles exist along a continuum that is repeated across all major projection systems, such as those for vision, motor control and cognition. The largest component of gene expression variation in the mouse thalamus is topographically organized, with features conserved in humans. Transcriptional differences between these thalamic neuronal identities are tied to cellular features that are critical for function, such as axonal morphology and membrane properties. Molecular profiling therefore reveals covariation in the properties of thalamic pathways serving all major input modalities and output targets, thus establishing a molecular framework for understanding the thalamus.


Assuntos
Córtex Cerebral/anatomia & histologia , Tálamo/anatomia & histologia , Potenciais de Ação , Animais , Atlas como Assunto , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiologia , Humanos , Camundongos , Camundongos Transgênicos , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Vias Neurais/fisiologia , Tálamo/metabolismo , Tálamo/fisiologia , Transcriptoma
10.
Nat Methods ; 16(10): 983-986, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31501545

RESUMO

Single-cell molecular profiling technologies are gaining rapid traction, but the manual process by which resulting cell types are typically annotated is labor intensive and rate-limiting. We describe Garnett, a tool for rapidly annotating cell types in single-cell transcriptional profiling and single-cell chromatin accessibility datasets, based on an interpretable, hierarchical markup language of cell type-specific genes. Garnett successfully classifies cell types in tissue and whole organism datasets, as well as across species.


Assuntos
Atlas como Assunto , Análise de Célula Única/métodos , Algoritmos , Animais , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Análise de Sequência de RNA/métodos , Transcrição Genética
11.
Science ; 365(6455)2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439762

RESUMO

Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then used our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a eukaryotic parasite and an open-access reference dataset for the study of malaria parasites.


Assuntos
Atlas como Assunto , Genes de Protozoários/fisiologia , Estágios do Ciclo de Vida/genética , Malária/parasitologia , Plasmodium berghei/genética , Plasmodium berghei/fisiologia , Transcriptoma , Animais , Anopheles/parasitologia , Células HeLa , Humanos , Plasmodium berghei/isolamento & purificação , Análise de Célula Única
12.
J Neurol ; 266(Suppl 1): 52-61, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31422454

RESUMO

Intravenous contrast agent-enhanced magnetic resonance imaging of the endolymphatic space (ELS) of the inner ear permits direct, in-vivo, non-invasive visualization of labyrinthine structures and thus verification of endolymphatic hydrops (ELH). However, current volumetric assessment approaches lack normalization. The aim of this study was to develop a probabilistic atlas of the inner ear's bony labyrinth as a first step towards an automated and reproducible volume-based quantification of the ELS. The study included three different datasets: a source dataset (D1) to build the probabilistic atlas and two testing sets (D2, D3). D1 included 24 right-handed patients (12 females; mean age 51.5 ± 3.9 years) and D2 5 patients (3 female; mean age 48.8 ± 5.01 years) with vestibular migraine without ELH or any measurable vestibular deficits. D3 consisted of five patients (one female; mean age 46 ± 5.2 years) suffering from unilateral Menière's disease and ELH. Data processing comprised three steps: preprocessing using an affine and deformable fusion registration pipeline, computation of an atlas for the left and right inner ear using a label-assisted approach, and validation of the atlas based on localizing and segmenting previously unseen ears. The three-dimensional probabilistic atlas of the inner ear's bony labyrinth consisted of the internal acoustic meatus and inner ears (including cochlea, otoliths, and semicircular canals) for both sides separately. The analyses showed a high level of agreement between the atlas-based segmentation and the manual gold standard with an overlap of 89% for the right ear and 86% for the left ear (measured by dice scores). This probabilistic in vivo atlas of the human inner ear's bony labyrinth and thus of the inner ear's total fluid space for both ears represents a necessary step towards a normalized, easily reproducible and reliable volumetric quantification of the perilymphatic and endolymphatic space in view of MR volumetric assessment of ELH. The proposed atlas lays the groundwork for state-of-the-art approaches (e.g., deep learning) and will be provided to the scientific community.


Assuntos
Atlas como Assunto , Imageamento Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Vestíbulo do Labirinto/anatomia & histologia , Vestíbulo do Labirinto/diagnóstico por imagem , Adulto , Idoso , Orelha Interna/anatomia & histologia , Orelha Interna/diagnóstico por imagem , Endolinfa/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Adulto Jovem
13.
Brain Struct Funct ; 224(8): 2883-2897, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31444616

RESUMO

Quantifying the distribution of cells in every brain region is fundamental to attaining a comprehensive census of distinct neuronal and glial types. Until recently, estimating neuron numbers involved time-consuming procedures that were practically limited to stereological sampling. Progress in open-source image recognition software, growth in computing power, and unprecedented neuroinformatics developments now offer the potentially paradigm-shifting alternative of comprehensive cell-by-cell analysis in an entire brain region. The Allen Brain Atlas provides free digital access to complete series of raw Nissl-stained histological section images along with regional delineations. Automated cell segmentation of these data enables reliable and reproducible high-throughput quantification of regional variations in cell count, density, size, and shape at whole-system scale. While this strategy is directly applicable to any regions of the mouse brain, we first deploy it here on the closed-loop circuit of the hippocampal formation: the medial and lateral entorhinal cortices; dentate gyrus (DG); areas Cornu Ammonis 3 (CA3), CA2, and CA1; and dorsal and ventral subiculum. Using two independent image processing pipelines and the adult mouse reference atlas, we report the first cellular-level soma segmentation in every sub-region and non-principal layer of the left hippocampal formation through the full rostral-caudal extent. It is important to note that our techniques excluded the layers with the largest number of cells, DG granular and CA pyramidal, due to dense packing. The numerical estimates for the remaining layers are corroborated by traditional stereological sampling on a data subset and well match sparse published reports.


Assuntos
Hipocampo/citologia , Neuroglia/citologia , Neurônios/citologia , Animais , Atlas como Assunto , Contagem de Células , Técnicas Histológicas , Processamento de Imagem Assistida por Computador/métodos , Masculino , Camundongos Endogâmicos C57BL
14.
Brain Struct Funct ; 224(8): 2603-2617, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407103

RESUMO

The human eye movement network is a complex system that requires the integration of sensory, motor, attentional, and executive processes. Here, we review the neuroanatomy of the eye movement network with an emphasis on functional neuroimaging applications. We consolidate the literature into a concise resource designed to be immediately accessible and applicable to diverse research interests, and present the novel Functional Oculomotor System (FOcuS) Atlas-a tool in stereotaxic space that will simplify and standardize the inclusion of the eye movement network in future functional neuroimaging studies. We anticipate this review and the FOcuS Atlas will facilitate increased examination of the eye movement network across disciplines leading to a thorough understanding of how eye movement network function contributes to higher-order cognition and how it is integrated with other brain networks. Furthermore, functional examination of the eye movement network in patient populations offers the potential for deeper insight into the role of eye movement circuitry in functional network activity, diagnostic assessments, and the indications for augmentative communication systems that rely on eye movement control.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Movimentos Oculares , Atlas como Assunto , Encéfalo/diagnóstico por imagem , Neuroimagem Funcional , Humanos , Vias Neurais/fisiologia
15.
Nat Neurosci ; 22(8): 1371-1378, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285616

RESUMO

There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional subregions. To address this question, we employed a rich task battery designed to tap into a broad range of cognitive processes. During four functional MRI sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional subregions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. The new parcellation provides a functional atlas to guide future neuroimaging studies.


Assuntos
Cerebelo/diagnóstico por imagem , Cerebelo/fisiologia , Atlas como Assunto , Mapeamento Encefálico , Córtex Cerebelar/diagnóstico por imagem , Córtex Cerebelar/fisiologia , Movimentos Oculares , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Movimento/fisiologia , Neuroimagem , Desempenho Psicomotor/fisiologia , Adulto Jovem
16.
Nucleic Acids Res ; 47(15): 7842-7856, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31350901

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.


Assuntos
Recidiva Local de Neoplasia/genética , Neoplasias/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Fatores Etários , Atlas como Assunto , Grupos de Populações Continentais , Humanos , Anotação de Sequência Molecular , Metástase Neoplásica , Recidiva Local de Neoplasia/etnologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias/classificação , Neoplasias/etnologia , Neoplasias/mortalidade , RNA Longo não Codificante/classificação , RNA Longo não Codificante/metabolismo , RNA Mensageiro/classificação , RNA Mensageiro/metabolismo , Fatores Sexuais , Análise de Sobrevida
17.
Immunology ; 158(2): 70-84, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31347163

RESUMO

Recent advances in high-throughput molecular profiling technologies and multiplexed imaging platforms have revolutionized our ability to characterize the tumor immune microenvironment. As a result, studies of tumor-associated immune cells increasingly involve complex data sets that require sophisticated methods of computational analysis. In this review, we present an overview of key assays and related bioinformatics tools for analyzing the tumor-associated immune system in bulk tissues and at the single-cell level. In parallel, we describe how data science strategies and novel technologies have advanced tumor immunology and opened the door for new opportunities to exploit host immunity to improve cancer clinical outcomes.


Assuntos
Antígenos de Neoplasias/imunologia , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias/imunologia , Software , Microambiente Tumoral/imunologia , Antígenos de Neoplasias/genética , Atlas como Assunto , Citometria de Fluxo/métodos , Perfilação da Expressão Gênica , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Internet , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Imagem Molecular/métodos , Neoplasias/genética , Neoplasias/patologia , Análise de Célula Única/métodos , Microambiente Tumoral/genética
18.
Elife ; 82019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31339489

RESUMO

The central processing pathways of the human olfactory system are not fully understood. The olfactory bulb projects directly to a number of cortical brain structures, but the distinct networks formed by projections from each of these structures to the rest of the brain have not been well-defined. Here, we used functional magnetic resonance imaging and k-means clustering to parcellate human primary olfactory cortex into clusters based on whole-brain functional connectivity patterns. Resulting clusters accurately corresponded to anterior olfactory nucleus, olfactory tubercle, and frontal and temporal piriform cortices, suggesting dissociable whole-brain networks formed by the subregions of primary olfactory cortex. This result was replicated in an independent data set. We then characterized the unique functional connectivity profiles of each subregion, producing a map of the large-scale processing pathways of the human olfactory system. These results provide insight into the functional and anatomical organization of the human olfactory system.


Assuntos
Condutos Olfatórios/fisiologia , Adulto , Anatomia Artística , Atlas como Assunto , Feminino , Humanos , Masculino , Rede Nervosa/fisiologia , Córtex Olfatório/fisiologia
20.
Neuroimage ; 199: 651-662, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220576

RESUMO

The specificity and sensitivity of resting state functional MRI (rs-fMRI) measurements depend on preprocessing choices, such as the parcellation scheme used to define regions of interest (ROIs). In this study, we critically evaluate the effect of brain parcellations on machine learning models applied to rs-fMRI data. Our experiments reveal an intriguing trend: On average, models with stochastic parcellations consistently perform as well as models with widely used atlases at the same spatial scale. We thus propose an ensemble learning strategy to combine the predictions from models trained on connectivity data extracted using different (e.g., stochastic) parcellations. We further present an implementation of our ensemble learning strategy with a novel 3D Convolutional Neural Network (CNN) approach. The proposed CNN approach takes advantage of the full-resolution 3D spatial structure of rs-fMRI data and fits non-linear predictive models. Our ensemble CNN framework overcomes the limitations of traditional machine learning models for connectomes that often rely on region-based summary statistics and/or linear models. We showcase our approach on a classification (autism patients versus healthy controls) and a regression problem (prediction of subject's age), and report promising results.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Conectoma/métodos , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Atlas como Assunto , Encéfalo/fisiopatologia , Criança , Estudos de Coortes , Conectoma/normas , Humanos , Interpretação de Imagem Assistida por Computador/normas , Imagem por Ressonância Magnética/normas , Masculino , Adulto Jovem
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