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      Machine learning analysis of pregnancy data enables early identification of a subpopulation of newborns with ASD

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          Abstract

          To identify newborns at risk of developing ASD and to detect ASD biomarkers early after birth, we compared retrospectively ultrasound and biological measurements of babies diagnosed later with ASD or neurotypical (NT) that are collected routinely during pregnancy and birth. We used a supervised machine learning algorithm with a cross-validation technique to classify NT and ASD babies and performed various statistical tests. With a minimization of the false positive rate, 96% of NT and 41% of ASD babies were identified with a positive predictive value of 77%. We identified the following biomarkers related to ASD: sex, maternal familial history of auto-immune diseases, maternal immunization to CMV, IgG CMV level, timing of fetal rotation on head, femur length in the 3rd trimester, white blood cell count in the 3rd trimester, fetal heart rate during labor, newborn feeding and temperature difference between birth and one day after. Furthermore, statistical models revealed that a subpopulation of 38% of babies at risk of ASD had significantly larger fetal head circumference than age-matched NT ones, suggesting an in utero origin of the reported bigger brains of toddlers with ASD. Our results suggest that pregnancy follow-up measurements might provide an early prognosis of ASD enabling pre-symptomatic behavioral interventions to attenuate efficiently ASD developmental sequels.

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          The contribution of de novo coding mutations to autism spectrum disorder.

          Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.
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            End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography

            With an estimated 160,000 deaths in 2018, lung cancer is the most common cause of cancer death in the United States1. Lung cancer screening using low-dose computed tomography has been shown to reduce mortality by 20-43% and is now included in US screening guidelines1-6. Existing challenges include inter-grader variability and high false-positive and false-negative rates7-10. We propose a deep learning algorithm that uses a patient's current and prior computed tomography volumes to predict the risk of lung cancer. Our model achieves a state-of-the-art performance (94.4% area under the curve) on 6,716 National Lung Cancer Screening Trial cases, and performs similarly on an independent clinical validation set of 1,139 cases. We conducted two reader studies. When prior computed tomography imaging was not available, our model outperformed all six radiologists with absolute reductions of 11% in false positives and 5% in false negatives. Where prior computed tomography imaging was available, the model performance was on-par with the same radiologists. This creates an opportunity to optimize the screening process via computer assistance and automation. While the vast majority of patients remain unscreened, we show the potential for deep learning models to increase the accuracy, consistency and adoption of lung cancer screening worldwide.
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              Global Prevalence of Autism and Other Pervasive Developmental Disorders

              We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries. Autism Res 2012, 5: 160–179. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                ben-ari@neurochlore.fr
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                25 March 2021
                25 March 2021
                2021
                : 11
                : 6877
                Affiliations
                [1 ]Gynecology-Obstetrics Department, Mère-Enfant Hospital, University Hospital Center, Limoges, France
                [2 ]BABiomedical, Luminy Scientific Campus, Marseille, France
                [3 ]GRID grid.429754.9, Neurochlore, ; Luminy Scientific Campus, Marseille, France
                [4 ]GRID grid.31151.37, Bacteriology-Virology-Hygiene Department, , University Hospital Center, ; Limoges, France
                [5 ]GRID grid.31151.37, French National Reference Center for Herpes Viruses, , University Hospital Center, ; Limoges, France
                [6 ]GRID grid.412212.6, ISNI 0000 0001 1481 5225, Department of Biochemistry and Molecular Genetics, , Dupuytren University Hospital, ; Limoges, France
                [7 ]GRID grid.507621.7, INRAE, UMR MIA 518, , INRA AgroParisTech Université Paris-Saclay, ; Paris, France
                [8 ]GRID grid.38142.3c, ISNI 000000041936754X, Martinos Center for Biomedical Imaging, , Harvard Medical School, ; Boston, USA
                [9 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Gillberg Neuropsychiatry Center, Sahlgrenska Academy, , Gothenburg University, ; Gothenburg, Sweden
                [10 ]GRID grid.31151.37, Autism Expert Center and Autism Resource Center of Limousin, , University Hospital Center, ; Limoges, France
                Article
                86320
                10.1038/s41598-021-86320-0
                7994821
                33767300
                326c0309-5dfa-48ae-8509-7168d7b39a10
                © The Author(s) 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 August 2020
                : 10 March 2021
                Categories
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                Custom metadata
                © The Author(s) 2021

                Uncategorized
                machine learning,data mining,statistical methods,autism spectrum disorders
                Uncategorized
                machine learning, data mining, statistical methods, autism spectrum disorders

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