STORMSeq: an open-source, user-friendly pipeline for processing personal genomics data in the cloud.

The increasing public availability of personal complete genome sequencing data has ushered in an era of democratized genomics. However, read mapping and variant calling software is constantly improving and individuals with personal genomic data may prefer to customize and update their variant calls. Here, we describe STORMSeq (Scalable Tools for Open-Source Read Mapping), a graphical interface cloud computing solution that does not require a parallel computing environment or extensive technical experience.

Using molecular features of xenobiotics to predict hepatic gene expression response.

Despite recent advances in molecular medicine and rational drug design, many drugs still fail because toxic effects arise at the cellular and tissue level. In order to better understand these effects, cellular assays can generate high-throughput measurements of gene expression changes induced by small molecules. However, our understanding of how the chemical features of small molecules influence gene expression is very limited.

A novel signal detection algorithm for identifying hidden drug-drug interactions in adverse event reports.

Objective: Adverse drug events (ADEs) are common and account for 770 000 injuries and deaths each year and drug interactions account for as much as 30% of these ADEs. Spontaneous reporting systems routinely collect ADEs from patients on complex combinations of medications and provide an opportunity to discover unexpected drug interactions. Unfortunately, current algorithms for such "signal detection" are limited by underreporting of interactions that are not expected.

Detecting drug interactions from adverse-event reports: interaction between paroxetine and pravastatin increases blood glucose levels.

The lipid-lowering agent pravastatin and the antidepressant paroxetine are among the most widely prescribed drugs in the world. Unexpected interactions between them could have important public health implications. We mined the US Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) for side-effect profiles involving glucose homeostasis and found a surprisingly strong signal for comedication with pravastatin and paroxetine.

Bioinformatics challenges for personalized medicine.

Motivation: Widespread availability of low-cost, full genome sequencing will introduce new challenges for bioinformatics.

Results: This review outlines recent developments in sequencing technologies and genome analysis methods for application in personalized medicine. New methods are needed in four areas to realize the potential of personalized medicine: (i) processing large-scale robust genomic data; (ii) interpreting the functional effect and the impact of genomic variation; (iii) integrating systems data to relate complex genetic interactions with phenotypes; and (iv) translating these discoveries into medical practice.

Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets.

Understanding the neuropathology of multiple sclerosis (MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser-capture microdissection and proteomics, proteins unique to three major types of MS lesions: acute plaque, chronic active plaque and chronic plaque.

Genome-wide network analysis reveals the global properties of IFN-beta immediate transcriptional effects in humans.

IFN-beta effectively controls clinical exacerbations and magnetic resonance imaging activity in most multiple sclerosis patients. However, its mechanism of action has not been yet fully elucidated. In this study we used DNA microarrays to analyze the longitudinal transcriptional profile of blood cells within a week of IFN-beta administration.

Mapping gene activity in complex disorders: Integration of expression and genomic scans for multiple sclerosis.

Genetic predisposition contributes to the pathogenesis of most common diseases. Genetic studies have been extremely successful in the identification of genes responsible for a number of Mendelian disorders. However, with a few exceptions, genes predisposing to diseases with complex inheritance remain unknown despite multiple efforts.

Acceptance of home and clinic-based cystic fibrosis carrier education and testing by first, second, and third degree relatives of cystic fibrosis patients.

We contacted and offered free cystic fibrosis (CF) carrier education and testing to the first, second, and third degree relatives of individuals with CF followed at a large Southeastern US CF Clinic. Relatives were offered CF carrier education and testing either in their homes or in a genetic counseling clinic. Overall, of 514 relatives offered free CF carrier education and testing, 299 (58%) accepted.

Proband and parent assistance in identifying relatives for cystic fibrosis carrier testing.

To identify, contact, and offer free cystic fibrosis (CF) carrier education, testing, and genetic counseling to the first, second, and third degree relatives of individuals with CF, study personnel contacted probands or the parents of minor probands requesting assistance in identifying relatives. We requested family pedigrees, including names, addresses, and phone numbers and if necessary a saliva sample for determination of the specific CF mutations in the family. Two hundred three families of 220 probands being followed at a large CF clinic in the Southeastern United States were eligible for inclusion in the study.

Microtubular discontinuities as acquired ciliary defects in airway epithelium of patients with chronic respiratory diseases.

A critical relationship exists between ordered ciliary ultrastructure and optimal mucociliary clearance in the respiratory airways. Structurally defective cilia derived from heritable syndromes or from epithelial cell injury may promote or exacerbate chronic disease processes. A lesion of airway epithelial cilia characterized by microtubular discontinuities and previously associated with primary ciliary dyskinesia (PCD) has been documented in other forms of chronic airways diseases, including cystic fibrosis (CF).

Cystic fibrosis: a current review.

Cystic fibrosis (CF) is the most common severe genetic disorder seen in Caucasians. Defective exocrine gland secretions result in chronic diseases of the respiratory and gastrointestinal systems. However, the CF gene recently has been located and cloned.

Epidemic pneumonia in university students.

Longitudinal surveillance of pneumonia in a university student health service was conducted from 1965-1971 and 1984-1987. Of 104 pneumonia cases documented by chest x-ray, only six were presumed to have bacterial etiology; the remaining 98 were characteristic of atypical pneumonia syndrome. Mycoplasma pneumoniae was the etiology in 51% of the pneumonias in the 1960s and 13% in 1984-1987.

Chronic lung disease in children referred to a teaching hospital.

Etiology, symptomatology, and host factors were studied in 184 children referred to a teaching hospital for evaluation in an attempt to classify chronic or potentially chronic lung disease. A standardized historical questionnaire, physical findings, chest radiographs, and a laboratory panel identified a diagnosis that could be related directly or indirectly to chronic lung disease in 22% of the subjects. Among the remaining 78%, bronchiectasis was found in 9%, chronic pneumonia in 9%, chronic diseases with wheezing in 56%, and no significant lower respiratory disease in 4%.

Immunologic mechanisms suggested in the association of M. pneumoniae infection and extrapulmonary disease: a review.

Numerous case reports and retrospective studies suggest an association between M. pneumoniae respiratory infection and extrapulmonary complications, the most common of which involve the central nervous system. There is insufficient evidence based on prospective, carefully controlled observations to confirm this association at the present time.

Immunological interactions between host cells and mycoplasmas: an introduction.

In addition to eliciting host immune responses, many mycoplasmas interact nonspecifically with host cells. Early reports revealed peculiar inhibitory and stimulatory effects of mycoplasmas on the immune response in vivo; several investigators have now clearly defined nonspecific stimulation of B and T lymphocytes and also a nonspecific immunosuppressive effect on experimental animals and humans. These interactions relate to attachment of mycoplasmas to host cell membranes and perhaps involve sharing of membrane components.

The longitudinal approach to the pathogenesis of respiratory disease.

Longitudinal observations were made of a well-defined population of children at a day care center in an investigation of the pathogenesis of infections due to respiratory syncytial virus (RSV) and Mycoplasma pneumoniae. A single RSV infection induced a modest but significant degree of resistance to further RSV infection in these children. Age and immunity seemed to interact to decrease the intensity of the clinical expression of illness associated with RSV infection.