Browsing by Author "Rasga, Celia"
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- An integrative system biology approach to delineate complex genotype-phenotype associations in Autism Spectrum DisorderPublication . Asif, M; Martiniano, Hugo F.; Rasga, Celia; Marques, Ana R.; Santos, Joao X.; O., Guiomar; Couto, Francisco M.; Vicente, Astrid M.Introduction: Autism Spectrum Disorder (ASD) is characterized by deficits in social interaction and communication, and by the presence of repetitive behavior and/or restricted interests. ASD manifests with heterogeneous phenotype and has an estimated global prevalence of ~1%;- ASD is difficult to diagnose in very young children. Delayed diagnosis leads to delay in applying behavioral therapies that may help to reduce symptoms, particularly when applied at young age; - Copy Number Variant (CNV) screening has been widely used for primary diagnosis purposes and is associated with phenotypic variability in ASD patients; - Large scale studies have identified hundreds of ASD implicated loci; however, mechanistic and clinical interpretation of these disease-causing variants remains elusive.
- Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU studyPublication . Guillon, Quentin; Baduel, Sophie; Bejarano-Martín, Álvaro; Canal-Bedia, Ricardo; MagÁn-Maganto, María; FernÁndez-Álvarez, Clara; Martín-Cilleros, María Victoria; SÁnchez-Gómez, María Cruz; García-Primo, Patricia; Rose-Sweeney, Mary; Boilson, Andrew; LinertovÁ, Renata; Roeyers, Herbert; Van der Paelt, Sara; Schendel, Diana; Warberg, Christine Kloster; Cramer, Susanne; Narzisi, Antonio; Muratori, Filippo; Scattoni, María Luisa; Moilanen, Irma; Yliherva, Anneli; Saemundsen, Evald; Jonsdottir, Sigridur Loa; Efrim-Budisteanu, Magdalena; Arghir, Aurora; Papuc, Sorina Mihaela; Vicente, Astrid; Rasga, Celia; Xenia Kafka, Johanna; Poustka, Luise; Kothgassner, Oswald D.; Kawa, Rafal; Pisula, Ewa; Sellers, Tracey; Posada de la Paz, Manuel; Rogé, BernadetteProfessional guidance and support in response to first concerns appears to be an important predictor of the level of satisfaction with the detection process of autism in young children. In this study, we analyzed the views of 1342 family members, including 1278 parents, who completed an online survey form collecting information about their experience and satisfaction with the early detection of autism in their child. Specifically, we were interested in how specific experiences with the detection process relate to the satisfaction with it and whether we could identify important predictors of satisfaction. The detection process is an emotionally charged period for parents, often described as painful, chaotic, and lengthy. A better understanding of their experiences is important to take appropriate action to improve the detection process. In our sample, the level of satisfaction with the detection process varied greatly from one respondent to another. Among the different experiences we considered, whether or not respondents received professional guidance and support in response to first concerns explained most of this variation. We also found that difficulty finding information about detection services, lack of professional guidance and support in response to first concerns, having to find a diagnostic service on one's own, and longer delays between confirmation of concerns and first appointment with a specialist were experiences associated with a greater likelihood of being unsatisfied. The findings of this study highlight the importance of the parent-professional relationship in the detection process and have important practical implications for health administrations to improve the detection process.
- Identification of biological mechanisms underlying a multidimensional ASD phenotype using machine learningPublication . Asif, Muhammad; Martiniano, Hugo F.M.C.; Marques, Ana Rita; Santos, João Xavier; Vilela, Joana; Rasga, Celia; Oliveira, Guiomar; Couto, Francisco M.; Vicente, Astrid M.The complex genetic architecture of Autism Spectrum Disorder (ASD) and its heterogeneous phenotype makes molecular diagnosis and patient prognosis challenging tasks. To establish more precise genotype-phenotype correlations in ASD, we developed a novel machine-learning integrative approach, which seeks to delineate associations between patients' clinical profiles and disrupted biological processes, inferred from their copy number variants (CNVs) that span brain genes. Clustering analysis of the relevant clinical measures from 2446 ASD cases in the Autism Genome Project identified two distinct phenotypic subgroups. Patients in these clusters differed significantly in ADOS-defined severity, adaptive behavior profiles, intellectual ability, and verbal status, the latter contributing the most for cluster stability and cohesion. Functional enrichment analysis of brain genes disrupted by CNVs in these ASD cases identified 15 statistically significant biological processes, including cell adhesion, neural development, cognition, and polyubiquitination, in line with previous ASD findings. A Naive Bayes classifier, generated to predict the ASD phenotypic clusters from disrupted biological processes, achieved predictions with a high precision (0.82) but low recall (0.39), for a subset of patients with higher biological Information Content scores. This study shows that milder and more severe clinical presentations can have distinct underlying biological mechanisms. It further highlights how machine-learning approaches can reduce clinical heterogeneity by using multidimensional clinical measures, and establishes genotype-phenotype correlations in ASD. However, predictions are strongly dependent on patient's information content. Findings are therefore a first step toward the translation of genetic information into clinically useful applications, and emphasize the need for larger datasets with very complete clinical and biological information.
- Maternal CNV transmission to sons with autism correlates with phenotypic traits in the Broad Autism PhenotypePublication . Vicente, A.M.; Asif, Muhammad; Conceição, Inês; Kwiatkowska, Katarzyna; Rasga, Celia; Oliveira, Guiomar; Sousa, Lisete; Couto, FranciscoAutism Spectrum Disorder (ASD): Common neurodevelopmental disorder, global prevalence ~1 %; Persistent deficits in social communication and social interaction; restricted and repetitive behavior, interests, or activities – highly heterogeneous clinical presentation; Male to female ratio ~4:1.
- Translating the complex ASD genetic architecture into clinical phenotype using an integrative system biology approachPublication . Asif, M.; Martiniano, Hugo F.; Rasga, Celia; Marques, Ana R.; Santos, João X.; Couto, Francisco M.; Vicente, A.M.Objective: The global objective of this study is to improve ASD diagnosis and prognosis by dissecting the complex genotype-phenotype associations using an integrative systems biology approach.