Gene/Protein Disease Symptom Drug Enzyme Compound
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Statistical model checking techniques have been shown to be effective for approximate model checking on large stochastic systems, where explicit representation of the state space is impractical. Importantly, these techniques ensure the validity of results with statistical guarantees on errors. There is an increasing interest in these classes of algorithms in computational systems biology since analysis using traditional model checking techniques does not scale well. In this context, we present two improvements to existing statistical model checking algorithms. Firstly, we construct an algorithm which removes the need of the user to define the indifference region, a critical parameter in previous sequential hypothesis testing algorithms. Secondly, we extend the algorithm to account for the case when there may be a limit on the computational resources that can be spent on verifying a property; i.e, if the original algorithm is not able to make a decision even after consuming the available amount of resources, we resort to a p-value based approach to make a decision. We demonstrate the improvements achieved by our algorithms in comparison to current algorithms first with a straightforward yet representative example, followed by a real biological model on cell fate of gustatory neurons with microRNAs.
BMC Bioinformatics 2012
PMID:Improved statistical model checking methods for pathway analysis. 2328 74

The negative symptoms of schizophrenia, avolition, alogia, apathy and impaired or nonexistent social functioning, are strongly correlated with the progressive course and long-term prognosis of the disease, undermining the patient's ability to integrate socially, interpersonal skills and quality of life. At a time when new drug strategies are being developed, a better understanding of the etiology and pathogenesis underpinning the occurrence of negative symptoms constitutes an essential prerequisite for real therapeutic advances. Approaching this vulnerability from the neurodevelopmental perspective is especially pertinent with regard to the experimental studies conducted in animals. Several models have been put forward, involving a variety of topics such as the deleterious impact of a prenatal infection or of early maternal deprivation on brain development, or else the consequences of trauma and abuse suffered during childhood. These various models are based on biological abnormalities that could guide the identification of new therapeutic targets. They notably include the hyperreactivity of the hypothalamic-pituitary-adrenal axis and dysfunction of corticostriatal glutamatergic transmission. As such, in the traumagenic model, which associates neurodevelopmental and neurodegenerative processes, the dysfunction of corticostriatal glutamatergic transmission, by reducing the tonic dopamine release, could be the cause of an increase in the phasic dopamine release linked to stress. This excessive phasic response to stress may induce cerebral damage by increasing excitotoxicity and oxidative stress.
BMC Psychiatry 2014 Mar 26
PMID:Neurodevelopmental and environmental hypotheses of negative symptoms of schizophrenia. 2467 Feb 12

Non-alcoholic fatty liver disease (NAFLD) has emerged as a common cause of liver-related morbidity and mortality. Tackling this condition at a societal level will require a clear understanding of the burden of disease in the general population. However, a major limitation of such an assessment, particularly in a real-world setting, is the low rate of diagnosis of the condition, as recently identified by Alexander et al. (BMC Med 16:130, 2018). Therein, the likelihood that the condition is indeed underdiagnosed and the potential causes for such underdiagnosis are discussed. The authors underscore the need for physician education and for development of simple evaluation tools that are both robust and implementable in a primary care setting, along with effective therapeutics to overcome this apathy towards NAFLD. Importantly, there remains a need for additional data on the prevalence of non-alcoholic steatohepatitis, the more aggressive form of NAFLD, especially with progressive fibrosis, along with patient outcomes to inform health policy decisions related to screening, surveillance, and access to therapeutics.
BMC Med 2018 08 24
PMID:Putting non-alcoholic fatty liver disease on the radar for primary care physicians: how well are we doing? 3009 68