1. Agarwal S, Yu H, Kohane I. {{BioNOT: A searchable database of biomedical negated sentences}}. {BMC Bioinformatics};2011 (Oct 27);12(1):420.
ABSTRACT: BACKGROUND: Negated biomedical events are often ignored by text-mining applications; however, such events carry scientific significance. We report on the development of BioNOT, a database of negated sentences that can be used to extract such negated events. Description: Currently BioNOT incorporates ~32 million negated sentences, extracted from over 336 million biomedical sentences from three resources: ~2 million full-text biomedical articles in Elsevier and the PubMed Central, as well as ~20 million abstracts in PubMed. We evaluated BioNOT on three important genetic disorders: autism, Alzheimer’s disease and Parkinson’s disease, and found that BioNOT is able to capture negated events that may be ignored by experts. CONCLUSIONS: The BioNOT database can be a useful resource for biomedical researchers. BioNOT is freely available at http://bionot.askhermes.org/. In future work, we will develop semantic web related technologies to enrich BioNOT.
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2. Bruno DL, White SM, Ganesamoorthy D, Burgess T, Butler K, Corrie S, Francis D, Hills L, Prabhakara K, Ngo C, Norris F, Oertel R, Pertile MD, Stark Z, Amor DJ, Slater HR. {{Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping}}. {J Med Genet};2011 (Oct 29)
BackgroundSeveral recent studies have demonstrated the use of single nucleotide polymorphism (SNP) arrays for the investigation of intellectual disability, developmental delay, autism or congenital abnormalities. In addition to LogR ‘copy number’ data, these arrays provide SNP genotyping data for gene level autozygosity mapping, estimating low levels of mosaicism, assessing long continuous stretches of homozygosity (LCSH), detection of uniparental disomy, and ‘autozygous’ regions. However, there remains little specific information on the clinical utility of this genotyping data.MethodsMolecular karyotyping, using SNP array, was performed on 5000 clinical samples.ResultsClinically significant ‘LogR neutral’ genotyping abnormalities were detected in 0.5% of cases. Among these were a single case of chimerism, 12 cases with low level chromosome mosaicism, and 11 cases with an LCSH associated with uniparental disomy. In addition, the genotyping data revealed several LCSH associated with clinically relevant ‘recessive type’ genetic defects.ConclusionsThese results demonstrate the utility of SNP genotyping data for detection of clinically significant abnormalities, including chimerism/mosaicism and recessive Mendelian disorders associated with autozygosity. The incidence of clinically significant low level mosaicism inferred from these cases suggests that this has hitherto been underestimated and chromosome mosaicism frequently occurs in the absence of indicative clinical features. The growing appreciation among clinicians and demand for SNP genotyping data poses significant challenges for the interpretation of LCSH, especially where there is no detailed phenotypic description to direct laboratory analysis. Finally, reporting of unexpected or hidden consanguinity revealed by SNP array analysis raises potential ethical and legal issues.
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3. Jiao Y, Chen R, Ke X, Cheng L, Chu K, Lu Z, Herskovits EH. {{Predictive models for subtypes of autism spectrum disorder based on single-nucleotide polymorphisms and magnetic resonance imaging}}. {Adv Med Sci};2011 (Oct 29):1-9.
Purpose: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, of which Asperger syndrome and high-functioning autism are subtypes. Our goal is: 1) to determine whether a diagnostic model based on single-nucleotide polymorphisms (SNPs), brain regional thickness measurements, or brain regional volume measurements can distinguish Asperger syndrome from high-functioning autism; and 2) to compare the SNP, thickness, and volume-based diagnostic models.Material and Methods: Our study included 18 children with ASD: 13 subjects with high-functioning autism and 5 subjects with Asperger syndrome. For each child, we obtained 25 SNPs for 8 ASD-related genes; we also computed regional cortical thicknesses and volumes for 66 brain structures, based on structural magnetic resonance (MR) examination. To generate diagnostic models, we employed five machine-learning techniques: decision stump, alternating decision trees, multi-class alternating decision trees, logistic model trees, and support vector machines.Results: For SNP-based classification, three decision-tree-based models performed better than the other two machine-learning models. The performance metrics for three decision-tree-based models were similar: decision stump was modestly better than the other two methods, with accuracy = 90%, sensitivity = 0.95 and specificity = 0.75. All thickness and volume-based diagnostic models performed poorly. The SNP-based diagnostic models were superior to those based on thickness and volume. For SNP-based classification, rs878960 in GABRB3 (gamma-aminobutyric acid A receptor, beta 3) was selected by all tree-based models.Conclusion: Our analysis demonstrated that SNP-based classification was more accurate than morphometry-based classification in ASD subtype classification. Also, we found that one SNP-rs878960 in GABRB3-distinguishes Asperger syndrome from high-functioning autism.
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4. Meaux E, Gillet P, Bonnet-Brilhault F, Barthelemy C, Batty M. {{Les anomalies du traitement des emotions faciales dans l’autisme : un trouble de la perception globale}}. {Encephale};2011 (Oct);37(5):371-378.
INTRODUCTION: Autistic syndrome is defined by several abnormalities, mainly affecting social interaction skills. Disorders of the processes of processing facial and emotional stimuli, and particularly avoidance of gaze, have also been reported in this disorder. Some authors have suggested that these abnormalities may be explained, or at least contributed to, by the social disorder observed in this syndrome. The aim of this study was therefore to improve the understanding of the processes involved in perception AND the representation of faces expressing emotion in subjects with autism spectrum disorders (ASDs). METHODS: Eleven children with ASDs (mean developmental age 7 years 11 months) and eleven normally developing children (mean age 7 years 9 months) took part in three experiments. The first involved overall discrimination of emotions using photographs of faces expressing six basic emotions, the second required local emotional discrimination on the basis of isolated elements of the face (photographs of eyes and mouths isolated from the rest of the face), and for the third the children were asked to create faces expressing emotions by means of a jig-saw puzzle format, using photographs of isolated elements of the face (overall representation necessitating local discrimination). RESULTS: Our findings revealed that the normally developing children had difficulties with the process of local discrimination of emotions: their performance improved when overall perception was possible. In contrast, and astonishingly, the children with ASD were more able to discriminate isolated eyes expressing emotion than the controls, but their performance declined when overall processing was required. DISCUSSION: Our results suggested that the emotional disorders observed in ASDs might be explained by greater skills in the processing of local information. This might explain the inability of children with ASDs to achieve coherent perception of their social environment and might also lead to the withdrawal that is characteristic of this disorder. These results also suggest that the gaze avoidance that is characteristic of individuals with ASDs is eliminated when eyes are presented alone. This gaze avoidance therefore seems to be related to the complexity and variability of this type of stimulus and not to the social nature of the stimulus.
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5. Pascolo PB, Cattarinussi A. {{On the relationship between mouth opening and « broken mirror neurons » in autistic individuals}}. {J Electromyogr Kinesiol};2011 (Oct 29)
Electromyographies of the mylohyoid muscle (MH) during the execution of the goal-oriented action « grasping to eat » have been used to determine the time relationship between the opening of the mouth and the beginning of the movement. This has been used to distinguish the behaviour of typical developing (TD) children from that of highly functioning autistic (ASD) individuals. The results of previous studies appeared to provide evidence of a deficit in action chain organization in ASD subjects and prompted the hypothesis of a « broken » mirror neuron system (MNS) for these individuals. Our results show the MH activation timing is not reliable in discriminating between TD and ASD children and the distance between the food and the subject plays a key role on the MH activation timing and cannot be neglected when analysing these type of data. The preliminary investigation on the effects of external perturbations also shows that these might have an effect on the results and further investigations are warranted. It appears that there is not enough evidence to support a link between ASD and a broken mirror network system (MNS), and the experimental results must be carefully interpreted before developing therapeutic or rehabilitative protocols.
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6. van Tongerloo MA, Bor HH, Lagro-Janssen AL. {{Detecting Autism Spectrum Disorders in the General Practitioner’S Practice}}. {J Autism Dev Disord};2011 (Oct 29)
It takes considerable time before Autism Spectrum Disorders are diagnosed. Validated diagnostic instruments are available, but not applicable to primary healthcare. By means of a case-control study we investigated whether there were differences in presented complaints and referral patterns between children with ASD (n = 49) and a control group of children without ASD (n = 81). Children with ASD were often presented as crybabies and often showed feeding problems. They visited the GP’s surgery more often with anxiety disorders, enuresis, and sleeping disorders. They were referred more often to physiotherapists and speech-therapists and had tympanostomy tubes and tonsillectomies more often. Depression in the parents of children with ASD was remarkably prevalent.
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7. Wiggins JL, Bedoyan JK, Peltier SJ, Ashinoff S, Carrasco M, Weng SJ, Welsh RC, Martin DM, Monk CS. {{The impact of serotonin transporter (5-HTTLPR) genotype on the development of resting-state functional connectivity in children and adolescents: A preliminary report}}. {Neuroimage};2011 (Oct 18)
A fundamental component of brain development is the formation of large-scale networks across the cortex. One such network, the default network, undergoes a protracted development, displaying weak connectivity in childhood that strengthens in adolescence and becomes most robust in adulthood. Little is known about the genetic contributions to default network connectivity in adulthood or during development. Alterations in connectivity between posterior and frontal portions of the default network have been associated with several psychological disorders, including anxiety, autism spectrum disorders, schizophrenia, depression, and attention-deficit/hyperactivity disorder. These disorders have also been linked to variants of the serotonin transporter linked polymorphic region (5-HTTLPR). The L(A) allele of 5-HTTLPR results in higher serotonin transporter expression than the S allele or the rarer L(G) allele. 5-HTTLPR may influence default network connectivity, as the superior medial frontal region has been shown to be sensitive to changes in serotonin. Also, serotonin as a growth factor early in development may alter large-scale networks such as the default network. The present study examined the influence of 5-HTTLPR variants on connectivity between the posterior and frontal structures and its development in a cross-sectional study of 39 healthy children and adolescents. We found that children and adolescents homozygous for the S allele (S/S, n=10) showed weaker connectivity in the superior medial frontal cortex compared to those homozygous for the L(A) allele (L(A)/L(A), n=13) or heterozygotes (S/L(A), S/L(G), n=16). Moreover, there was an age-by-genotype interaction, such that those with L(A)/L(A) genotype had the steepest age-related increase in connectivity between the posterior hub and superior medial frontal cortex, followed by heterozygotes. In contrast, individuals with the S/S genotype had the least age-related increase in connectivity strength. This preliminary report expands our understanding of the genetic influences on the development of large-scale brain connectivity and lays down the foundation for future research and replication of the results with a larger sample.
