Autism bio markers using metabolomics

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kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Autism bio markers using metabolomics

Postby kulkulkan » Mon Nov 10, 2014 10:43 pm

I was just thinking today that surely one can come up with 20 biomarkers in ASD with high sensitivity and specificity and use this to perhaps even come up with subtypes. Then saw this which is promising.

http://journals.plos.org/plosone/articl ... ne.0112445

Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children
Paul R. West, David G. Amaral, Preeti Bais, Alan M. Smith, Laura A. Egnash, Mark E. Ross, [...view 6 more...], Robert E. Burrier

Background
The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age.

Objectives
To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment.

Methods
Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD.

Results
A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set.

Conclusions
This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations.



kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: Autism bio markers using metabolomics

Postby kulkulkan » Mon Nov 10, 2014 10:47 pm

Already blogged on it. This guy is good.

http://questioning-answers.blogspot.ca/ ... s.html?m=1

kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: Autism bio markers using metabolomics

Postby kulkulkan » Tue Nov 11, 2014 1:34 am

I believe this is the most important NEW finding / metabolite which ranked #1 in two different models used in this study - Homocitrulline. It was low in ASD (as opposed to being high which is usually bad as mentioned below). Hope this spurs new research interest in this metabolite.

We also identified a new, previously undescribed potential ASD biomarker, homocitrulline. This metabolite was decreased in ASD patients and had the highest rank of all features in both SVM and PLS classification models. Homocitrulline is a poorly understood molecule which is known to be formed inside the mitochondria from lysine and carbamoyl phosphate. The decreased homocitrulline levels in the blood suggests that homocitrulline metabolism in the brain may also be disrupted, Homocitrulline levels are increased in urine and blood in patients with ornithine translocase (SLC25A15) deficiency which diverts carbamyl phosphate to react with lysine. These patients can exhibit behavioral abnormalities similar to ASD such as developmental delay, ataxia, spasticity, learning disabilities, cognitive deficits and/or unexplained seizures [57]. Rats treated with intracerebroventricular administration of homocitrulline are also observed to have disrupted brain redox status and energy metabolism [58], [59]. These observations suggest that elevated brain levels of homocitrulline are deleterious; however additional studies are needed to define the brain levels of homocitrulline and the potential role in the development of ASD.



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