High-performance integrated virtual environment (HIVE): a robust infrastructure for next-generation sequence data analysis.

The High-performance Integrated Virtual Environment (HIVE) is a distributed storage and compute environment designed primarily to handle next-generation sequencing (NGS) data. This multicomponent cloud infrastructure provides secure web access for authorized users to deposit, retrieve, annotate and compute on NGS data, and to analyse the outcomes using web interface visual environments appropriately built in collaboration with research and regulatory scientists and other end users. Unlike many massively parallel computing environments, HIVE uses a cloud control server which virtualizes services, not processes. It is both very robust and flexible due to the abstraction layer introduced between computational requests and operating system processes. The novel paradigm of moving computations to the data, instead of moving data to computational nodes, has proven to be significantly less taxing for both hardware and network infrastructure.The honeycomb data model developed for HIVE integrates metadata into an object-oriented model. Its distinction from other object-oriented databases is in the additional implementation of a unified application program interface to search, view and manipulate data of all types. This model simplifies the introduction of new data types, thereby minimizing the need for database restructuring and streamlining the development of new integrated information systems. The honeycomb model employs a highly secure hierarchical access control and permission system, allowing determination of data access privileges in a finely granular manner without flooding the security subsystem with a multiplicity of rules. HIVE infrastructure will allow engineers and scientists to perform NGS analysis in a manner that is both efficient and secure. HIVE is actively supported in public and private domains, and project collaborations are welcomed. Database URL: https://hive.biochemistry.gwu.edu.

Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality?

BACKGROUND: Phenylalanine and tyrosine are precursor amino acids required for the synthesis of dopamine, the main neurotransmitter implicated in the neurobiology of schizophrenia. Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. This study aimed to compare phenylalanine, tyrosine, and their ratio (a proxy for PAH function) in a relatively large sample of schizophrenia patients and healthy controls. METHODS: We measured non-fasting plasma phenylalanine and tyrosine in 950 schizophrenia patients and 1000 healthy controls. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine ratio between patients and controls. RESULTS: Compared to controls, schizophrenia patients had higher phenylalanine (p<0.0001) and phenylalanine: tyrosine ratio (p<0.0001) but tyrosine did not differ between the two groups (p = 0.596). CONCLUSIONS: Elevated phenylalanine and phenylalanine:tyrosine ratio in the blood of schizophrenia patients have to be replicated in longitudinal studies. The results may relate to an abnormal PAH function in schizophrenia that could become a target for novel preventative and interventional approaches.

Allergen Specific IgE, Number and Timing of Past Suicide Attempts, and Instability in Patients with Recurrent Mood Disorders.

Suicide and decompensation of mental illness peak in spring and, to a lesser extent, in fall. Several recent studies reported that suicide and decompensation peaks coincided with spring and fall aeroallergen peaks. Allergic symptoms occur as the result of a complex biochemical cascade initiated by IgE antibodies (sensitization) and allergens (triggers). Animal models have shown molecular/neurochemical changes in the brain, as well as relevant behavioral changes associated with this IgE-mediated biochemical cascade. These factors suggest that seasonal allergy could precipitate suicidality and mood instability. In the current study, we compared the prior suicide attempt and history of decompensation of mood disorders in allergen sensitive vs nonsensitive patients. Further, we compared the ratio of events (attempts and decompensations) during the allergy season to events occurring during the rest of the year. Patients with Major Depressive Disorder or Bipolar I or II Disorder (n=80) were studied. There were no statistical differences in any measurement performed between the allergen sensitive and nonsensitive patients. These negative results are not consistent with recent epidemiological studies supporting a predictive association between allergy and categorical measures of suicidality (ideation, attempts, and completion). Clinical samples are likely not adequate to study less than strong predictive associations with suicide and suicide risk factors.