Hierarchical cortical transcriptome disorganization in autism / M. V. LOMBARDO in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 29p. Titre : Hierarchical cortical transcriptome disorganization in autism Type de document : Texte imprimé et/ou numérique Auteurs : M. V. LOMBARDO, Auteur ; E. COURCHESNE, Auteur ; N. E. LEWIS, Auteur ; T. PRAMPARO, Auteur Article en page(s) : 29p. Langues : Anglais (eng) Mots-clés : Autism  Gene co-expression networks  Immune  Synapse  Systems biology  Transcriptome  Translation Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. METHODS: Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. RESULTS: We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. CONCLUSIONS: These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation. En ligne : http://dx.doi.org/10.1186/s13229-017-0147-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Hierarchical cortical transcriptome disorganization in autism [Texte imprimé et/ou numérique] / M. V. LOMBARDO, Auteur ; E. COURCHESNE, Auteur ; N. E. LEWIS, Auteur ; T. PRAMPARO, Auteur . - 29p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 29p. Mots-clés : Autism  Gene co-expression networks  Immune  Synapse  Systems biology  Transcriptome  Translation Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. METHODS: Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. RESULTS: We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. CONCLUSIONS: These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation. En ligne : http://dx.doi.org/10.1186/s13229-017-0147-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Measuring outcome in an early intervention program for toddlers with autism spectrum disorder: use of a curriculum-based assessment / Elizabeth C. BACON in Autism Research and Treatment, 2014 (2014)  

Public ISBD [article]  inAutism Research and Treatment > 2014 (2014) Titre : Measuring outcome in an early intervention program for toddlers with autism spectrum disorder: use of a curriculum-based assessment Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth C. BACON, Auteur ; S. DUFEK, Auteur ; L. SCHREIBMAN, Auteur ; Aubyn C. STAHMER, Auteur ; K. PIERCE, Auteur ; E. COURCHESNE, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Measuring progress of children with autism spectrum disorder (ASD) during intervention programs is a challenge faced by researchers and clinicians. Typically, standardized assessments of child development are used within research settings to measure the effects of early intervention programs. However, the use of standardized assessments is not without limitations, including lack of sensitivity of some assessments to measure small or slow progress, testing constraints that may affect the child's performance, and the lack of information provided by the assessments that can be used to guide treatment planning. The utility of a curriculum-based assessment is discussed in comparison to the use of standardized assessments to measure child functioning and progress throughout an early intervention program for toddlers with risk for ASD. Scores derived from the curriculum-based assessment were positively correlated with standardized assessments, captured progress masked by standardized assessments, and early scores were predictive of later outcomes. These results support the use of a curriculum-based assessment as an additional and appropriate method for measuring child progress in an early intervention program. Further benefits of the use of curriculum-based measures for use within community settings are discussed. En ligne : http://dx.doi.org/10.1155/2014/964704 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331 [article] Measuring outcome in an early intervention program for toddlers with autism spectrum disorder: use of a curriculum-based assessment [Texte imprimé et/ou numérique] / Elizabeth C. BACON, Auteur ; S. DUFEK, Auteur ; L. SCHREIBMAN, Auteur ; Aubyn C. STAHMER, Auteur ; K. PIERCE, Auteur ; E. COURCHESNE, Auteur. Langues : Anglais (eng) in Autism Research and Treatment > 2014 (2014) Index. décimale : PER Périodiques Résumé : Measuring progress of children with autism spectrum disorder (ASD) during intervention programs is a challenge faced by researchers and clinicians. Typically, standardized assessments of child development are used within research settings to measure the effects of early intervention programs. However, the use of standardized assessments is not without limitations, including lack of sensitivity of some assessments to measure small or slow progress, testing constraints that may affect the child's performance, and the lack of information provided by the assessments that can be used to guide treatment planning. The utility of a curriculum-based assessment is discussed in comparison to the use of standardized assessments to measure child functioning and progress throughout an early intervention program for toddlers with risk for ASD. Scores derived from the curriculum-based assessment were positively correlated with standardized assessments, captured progress masked by standardized assessments, and early scores were predictive of later outcomes. These results support the use of a curriculum-based assessment as an additional and appropriate method for measuring child progress in an early intervention program. Further benefits of the use of curriculum-based measures for use within community settings are discussed. En ligne : http://dx.doi.org/10.1155/2014/964704 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331

Naturalistic language sampling to characterize the language abilities of 3-year-olds with autism spectrum disorder / Elizabeth C. BACON in Autism, 23-3 (April 2019)  

Public ISBD [article]  inAutism > 23-3 (April 2019) . - p.699-712 Titre : Naturalistic language sampling to characterize the language abilities of 3-year-olds with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth C. BACON, Auteur ; S. OSUNA, Auteur ; E. COURCHESNE, Auteur ; K. PIERCE, Auteur Article en page(s) : p.699-712 Langues : Anglais (eng) Mots-clés : autism spectrum disorders  language  minimally verbal  preverbal Index. décimale : PER Périodiques Résumé : Characterization of language in naturalistic settings in autism spectrum disorder has been lacking, particularly at young ages, but such information is important for parents, teachers, and clinicians to better support language development in real-world settings. Factors contributing to this lack of clarity include conflicting definitions of language abilities, use of non-naturalistic standardized assessments, and restricted samples. The current study examined one of the largest datasets of naturalistic language samples in toddlers with autism spectrum disorder, and language delay and typically developing contrast groups at age 3. A range of indices including length of phrase, grammatical markings, and social use of language was assayed during a naturalistic observation of a parent-child play session. In contrast to historical estimates, results indicated only 3.7% of children with autism spectrum disorder used no words, and 34% were minimally verbal. Children with autism spectrum disorder and language delay exhibited similar usage of grammatical markings, although both were reduced compared to typically developing children. The greatest difference between autism spectrum disorder and language delay groups was the quantity of social language. Overall, findings highlight a range of language deficits in autism spectrum disorder, but also illustrate that the most severe level of impairments is not as common in naturalistic settings as previously estimated by standardized assessments. En ligne : http://dx.doi.org/10.1177/1362361318766241 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=392 [article] Naturalistic language sampling to characterize the language abilities of 3-year-olds with autism spectrum disorder [Texte imprimé et/ou numérique] / Elizabeth C. BACON, Auteur ; S. OSUNA, Auteur ; E. COURCHESNE, Auteur ; K. PIERCE, Auteur . - p.699-712. Langues : Anglais (eng) in Autism > 23-3 (April 2019) . - p.699-712 Mots-clés : autism spectrum disorders  language  minimally verbal  preverbal Index. décimale : PER Périodiques Résumé : Characterization of language in naturalistic settings in autism spectrum disorder has been lacking, particularly at young ages, but such information is important for parents, teachers, and clinicians to better support language development in real-world settings. Factors contributing to this lack of clarity include conflicting definitions of language abilities, use of non-naturalistic standardized assessments, and restricted samples. The current study examined one of the largest datasets of naturalistic language samples in toddlers with autism spectrum disorder, and language delay and typically developing contrast groups at age 3. A range of indices including length of phrase, grammatical markings, and social use of language was assayed during a naturalistic observation of a parent-child play session. In contrast to historical estimates, results indicated only 3.7% of children with autism spectrum disorder used no words, and 34% were minimally verbal. Children with autism spectrum disorder and language delay exhibited similar usage of grammatical markings, although both were reduced compared to typically developing children. The greatest difference between autism spectrum disorder and language delay groups was the quantity of social language. Overall, findings highlight a range of language deficits in autism spectrum disorder, but also illustrate that the most severe level of impairments is not as common in naturalistic settings as previously estimated by standardized assessments. En ligne : http://dx.doi.org/10.1177/1362361318766241 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=392

The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking / A. MOORE in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 19p. Titre : The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking Type de document : Texte imprimé et/ou numérique Auteurs : A. MOORE, Auteur ; M. WOZNIAK, Auteur ; A. YOUSEF, Auteur ; C. C. BARNES, Auteur ; D. CHA, Auteur ; E. COURCHESNE, Auteur ; K. PIERCE, Auteur Article en page(s) : 19p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Early identification  Eye tracking  Geometric preference  Social attention Index. décimale : PER Périodiques Résumé : Background: The wide range of ability and disability in ASD creates a need for tools that parse the phenotypic heterogeneity into meaningful subtypes. Using eye tracking, our past studies revealed that when presented with social and geometric images, a subset of ASD toddlers preferred viewing geometric images, and these toddlers also had greater symptom severity than ASD toddlers with greater social attention. This study tests whether this "GeoPref test" effect would generalize across different social stimuli. Methods: Two hundred and twenty-seven toddlers (76 ASD) watched a 90-s video, the Complex Social GeoPref test, of dynamic geometric images paired with social images of children interacting and moving. Proportion of visual fixation time and number of saccades per second to both images were calculated. To allow for cross-paradigm comparisons, a subset of 126 toddlers also participated in the original GeoPref test. Measures of cognitive and social functioning (MSEL, ADOS, VABS) were collected and related to eye tracking data. To examine utility as a diagnostic indicator to detect ASD toddlers, validation statistics (e.g., sensitivity, specificity, ROC, AUC) were calculated for the Complex Social GeoPref test alone and when combined with the original GeoPref test. Results: ASD toddlers spent a significantly greater amount of time viewing geometric images than any other diagnostic group. Fixation patterns from ASD toddlers who participated in both tests revealed a significant correlation, supporting the idea that these tests identify a phenotypically meaningful ASD subgroup. Combined use of both original and Complex Social GeoPref tests identified a subgroup of about 1 in 3 ASD toddlers from the "GeoPref" subtype (sensitivity 35%, specificity 94%, AUC 0.75.) Replicating our previous studies, more time looking at geometric images was associated with significantly greater ADOS symptom severity. Conclusions: Regardless of the complexity of the social images used (low in the original GeoPref test vs high in the new Complex Social GeoPref test), eye tracking of toddlers can accurately identify a specific ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are predictive of ASD at the individual subject level and thus potentially useful for various clinical applications (e.g., early identification, prognosis, or development of subtype-specific treatments). En ligne : http://dx.doi.org/10.1186/s13229-018-0202-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking [Texte imprimé et/ou numérique] / A. MOORE, Auteur ; M. WOZNIAK, Auteur ; A. YOUSEF, Auteur ; C. C. BARNES, Auteur ; D. CHA, Auteur ; E. COURCHESNE, Auteur ; K. PIERCE, Auteur . - 19p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 19p. Mots-clés : Autism spectrum disorder  Early identification  Eye tracking  Geometric preference  Social attention Index. décimale : PER Périodiques Résumé : Background: The wide range of ability and disability in ASD creates a need for tools that parse the phenotypic heterogeneity into meaningful subtypes. Using eye tracking, our past studies revealed that when presented with social and geometric images, a subset of ASD toddlers preferred viewing geometric images, and these toddlers also had greater symptom severity than ASD toddlers with greater social attention. This study tests whether this "GeoPref test" effect would generalize across different social stimuli. Methods: Two hundred and twenty-seven toddlers (76 ASD) watched a 90-s video, the Complex Social GeoPref test, of dynamic geometric images paired with social images of children interacting and moving. Proportion of visual fixation time and number of saccades per second to both images were calculated. To allow for cross-paradigm comparisons, a subset of 126 toddlers also participated in the original GeoPref test. Measures of cognitive and social functioning (MSEL, ADOS, VABS) were collected and related to eye tracking data. To examine utility as a diagnostic indicator to detect ASD toddlers, validation statistics (e.g., sensitivity, specificity, ROC, AUC) were calculated for the Complex Social GeoPref test alone and when combined with the original GeoPref test. Results: ASD toddlers spent a significantly greater amount of time viewing geometric images than any other diagnostic group. Fixation patterns from ASD toddlers who participated in both tests revealed a significant correlation, supporting the idea that these tests identify a phenotypically meaningful ASD subgroup. Combined use of both original and Complex Social GeoPref tests identified a subgroup of about 1 in 3 ASD toddlers from the "GeoPref" subtype (sensitivity 35%, specificity 94%, AUC 0.75.) Replicating our previous studies, more time looking at geometric images was associated with significantly greater ADOS symptom severity. Conclusions: Regardless of the complexity of the social images used (low in the original GeoPref test vs high in the new Complex Social GeoPref test), eye tracking of toddlers can accurately identify a specific ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are predictive of ASD at the individual subject level and thus potentially useful for various clinical applications (e.g., early identification, prognosis, or development of subtype-specific treatments). En ligne : http://dx.doi.org/10.1186/s13229-018-0202-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

---

1 (1 - 4 / 4)