Mining Phenotypes for Protein Function Prediction

Until very recently, phenotypes only very rarely were studied in a systematic manner. While ontologies for describing gene functions now have a 10 year long tradition, similar vocabularies for describing the phenotype of genes are only emerging now; similarly, the techniques for determining phenotypes on a large scale (especially RNAi) are available only for a few years, while genomic sequencing or gene expression studies are already established for a much longer time. In this talk, we describe results from a study for exploiting phenotype descriptions for protein function prediction. We used the data from PhenomicsDB, a phenotype database integrated from several publicly available data sources. Due to the lack of standardization, phenotypes in PhenomicsDB can only be viewed as text (short statements, abstracts, singular terms, ...). We clustered these texts and analyzed the corresponding gene clusters in terms of their coherence in functional annotation and their interconnectedness by protein-protein-interactions. We also devised a method for using the close similarity in their phenotype descriptions to predict the function of proteins. We show that this methods yields a very good precision at acceptable coverage

The CTRW in finance: Direct and inverse problems with some generalizations and extensions

We study financial distributions within the framework of the continuous time random walk (CTRW). We review earlier approaches and present new results related to overnight effects as well as the generalization of the formalism which embodies a non-Markovian formulation of the CTRW aimed to account for correlated increments of the return.Comment: 25 pages, 3 figures, Elsart, submitted for publicatio

High-excitation molecular gas in local luminous AGN hosts

We used the mm/sub-mm receivers on the James Clerk Maxwell Telescope (JCMT) to observe the CO J=3--2, 2--1 lines in five local, optically powerful AGN and the J=4--3 line in 3C 293 (a powerful radio galaxy). Luminous CO J=3--2 emission and high CO (3--2)/(1--0) intensity ratios are found in all objects, indicating highly excited molecular gas. In 3C 293 an exceptionally bright CO J=4--3 line is found which cannot be easily explained given its quiescent star-forming environment and low AGN X-ray luminosity. In this object shocks emanating from a well-known interaction of a powerful jet with a dense ISM may be responsible for the high excitation of its molecular gas on galaxy-wide scales. Star formation can readily account for the gas excitation in the rest of the objects, although high X-ray AGN luminosities can also contribute significantly in two cases. Measuring and eventually imaging CO line ratios in local luminous QSO hosts can be done by a partially completed ALMA during its early phases of commissioning, promising a sensitive probe of starburst versus AGN activity in obscured environments at high linear resolutions.Comment: 6 pages, 1 figure, Accepted for publication in Astronomy & Astrophysic

Simultaneous NIR/sub-mm observation of flare emission from SgrA*

We report on a successful, simultaneous observation and modeling of the sub-millimeter to near-infrared flare emission of the Sgr A* counterpart associated with the super-massive black hole at the Galactic center. Our modeling is based on simultaneous observations that have been carried out on 03 June, 2008 using the NACO adaptive optics (AO) instrument at the ESO VLT and the LABOCA bolometer at the APEX telescope. Inspection and modeling of the light curves show that the sub-mm follows the NIR emission with a delay of 1.5+/-0.5 hours. We explain the flare emission delay by an adiabatic expansion of the source components.Comment: 12 pages, 9 figures, 3 tables, in press with A&

Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany

Background Despite strong recommendations for colorectal cancer (CRC) screening, participation rates are low. Understanding factors that affect screening choices is essential to developing future screening strategies. Therefore, this study assessed patient willingness to use non-invasive stool or blood based screening tests after refusing colonoscopy. Methods Participants were recruited during regular consultations. Demographic, health, psychological and socioeconomic factors were recorded. All subjects were advised to undergo screening by colonoscopy. Subjects who refused colonoscopy were offered a choice of non-invasive tests. Subjects who selected stool testing received a collection kit and instructions; subjects who selected plasma testing had a blood draw during the office visit. Stool samples were tested with the Hb/Hp Complex Elisa test, and blood samples were tested with the Epi proColon® 2.0 test. Patients who were positive for either were advised to have a diagnostic colonoscopy. Results 63 of 172 subjects were compliant to screening colonoscopy (37%). 106 of the 109 subjects who refused colonoscopy accepted an alternative non-invasive method (97%). 90 selected the Septin9 blood test (83%), 16 selected a stool test (15%) and 3 refused any test (3%). Reasons for blood test preference included convenience of an office draw, overall convenience and less time consuming procedure. Conclusions 97% of subjects refusing colonoscopy accepted a non-invasive screening test of which 83% chose the Septin9 blood test. The observation that participation can be increased by offering non-invasive tests, and that a blood test is the preferred option should be validated in a prospective trial in the screening setting

Phenoclustering: online mining of cross-species phenotypes

Summary: Recently, several methods for analyzing phenotype data have been published, but only few are able to cope with data sets generated in different studies, with different methods, or for different species. We developed an online system in which more than 300 000 phenotypes from a wide variety of sources and screening methods can be analyzed together. Clusters of similar phenotypes are visualized as networks of highly similar phenotypes, inducing gene groups useful for functional analysis. This system is part of PhenomicDB, providing the world's largest cross-species phenotype data collection with a tool to mine its wealth of information

PhenomicDB: a new cross-species genotype/phenotype resource

Phenotypes are an important subject of biomedical research for which many repositories have already been created. Most of these databases are either dedicated to a single species or to a single disease of interest. With the advent of technologies to generate phenotypes in a high-throughput manner, not only is the volume of phenotype data growing fast but also the need to organize these data in more useful ways. We have created PhenomicDB (freely available at ), a multi-species genotype/phenotype database, which shows phenotypes associated with their corresponding genes and grouped by gene orthologies across a variety of species. We have enhanced PhenomicDB recently by additionally incorporating quantitative and descriptive RNA interference (RNAi) screening data, by enabling the usage of phenotype ontology terms and by providing information on assays and cell lines. We envision that integration of classical phenotypes with high-throughput data will bring new momentum and insights to our understanding. Modern analysis tools under development may help exploiting this wealth of information to transform it into knowledge and, eventually, into novel therapeutic approaches

Assessment of dysfunction in aortic regurgitation by stress-shortening relationship

Some patients with aortic regurgitation develop irreversible left ventricular dysfunction. The purpose of this study was to noninvasively examine left ventricular function in patients with aortic regurgitation by determining the end-systolic stress-shortening relationship using M-mode echocardiography. Ten normal volunteers and 10 patients with chronic, isolated aortic regurgitation were studied at rest and following load and inotropic alteration by cold pressor testing. The baseline ejection phase indices of ejection fraction and percent fractional shortening did not distinguish between normals and patients with aortic regurgitation (74.6% +/- 2.8% versus 67.0% +/- 4.2%, P = NS and 37.6% +/- 2.4% versus 31.6% +/- 2.7%, P = NS, respectively.) Endsystolic stress was significantly greater in patients with aortic regurgitation both at rest (107.8 +/- 11.6 dynes/cm2 x 10-3 versus 68.4 +/- 4.8 dynes/cm2 x 10-3, P 2 x 10-3 versus 80.1 +/- 4.0 dynes/cm2 x 10-3, P < 0.005). Normals showed increased fractional shortening in the presence of increasing end-systolic stress. Patients with aortic regurgitation showed decreased fractional shortening during increased stress. This response suggests either left ventricular dysfunction with increasing stress or decreased myocardial contractile reserve after cold pressor inotropic stimulation. End-systolic stress-percent fractional shortening relationship may be a sensitive indicator of early left ventricular dysfunction in patients with aortic regurgitation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25611/1/0000159.pd

Noninvasive quantification of jeopardized myocardial mass in dogs using 2-dimensional echocardiography and thallium-201 tomography

The evaluation of jeopardized myocardial mass is important in defining the effect of interventions during myocardial infarction. To quantitate the in vivo mass at risk, 2-dimensional echocardiography (2-D echo) and thallium-201 single-photon emission computed tomography (SPECT) was performed in 10 closed-chest dogs after circumflex coronary artery occlusion. The 2-D images were manually digitized to compute left ventricular (LV) mass using a modified Simpson's rule algorithm. This measure of LV mass correlated well with the actual LV mass (r = 0.97). Perfused myocardial mass was estimated from thallium SPECT images 4 hours after occlusion using a region-growing algorithm. After the dogs were killed, the jeopardized mass was outlined using a dual perfusion staining technique using triphenyltetrazolium chloride and Evans blue dye. The actual perfused mass was well estimated by the thallium images (r = 0.96). The noninvasively determined mass at risk was calculated as: 2-D mass -- thallium SPECT mass, and correlated well with the pathologically determined mass at risk (r = 0.91). Thus, the jeopardized mass may be determined noninvasively by using 2-D echo and thallium-201 tomography. This approach may provide further information regarding the effect of intervention therapy on jeopardized myocardium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25450/1/0000900.pd