Designing Patterns and Profiles for Faster HMM Search

Profile HMMs are powerful tools for modeling conserved motifs in proteins. They are widely used by search tools to classify new protein sequences into families based on domain architecture. However, the proliferation of known motifs and new proteomic sequence data poses a computational challenge for search, requiring days of CPU time to annotate an organism's proteome. It is highly desirable to speed up HMM search in large databases. We design PROSITE-like patterns and short profiles that are used as filters to rapidly eliminate protein-motif pairs for which a full profile HMM comparison does not yield a significant match. The design of the pattern-based filters is formulated as a multichoice knapsack problem. Profile-based filters with high sensitivity are extracted from a profile HMM based on their theoretical sensitivity and false positive rate. Experiments show that our profile-based filters achieve high sensitivity (near 100 percent) while keeping around 20times speedup with respect to the unfiltered search program. Pattern-based filters typically retain at least 90 percent of the sensitivity of the source HMM with 30-40times speedup. The profile-based filters have sensitivity comparable to the multistage filtering strategy HMMERHEAD and are faster in most of our experiments.     

Multi‐round virus filter integrity test sensitivity

Virus filtration is becoming increasingly prominent in biopharmaceutical recovery processes as a robust method to remove a broad range of virus types. Increasing batch sizes will require large numbers of individual virus filter elements operating in parallel. Before adopting a more complex strategy for managing the integrity testing of large assemblies of virus filters, it is important to understand the sensitivity of the forward flow diffusion test for a single filter and for multiple filters in a single housing. An approach has been developed to estimate the largest hole that could consistently go undetected in a single filter within a larger assembly of virus filters. The integrity test limited minimum log reduction value (LRV) is determined based on the size of the hole as a function of the number of filters in the housing. This minimum LRV is shown to be largely insensitive to the number of filters within the housing. The likelihood of such damage occurring is expected to be very low. This analysis suggests there is minimal benefit to placing filters in individual housings or to adjusting the test specification to compensate for larger numbers of filters in a given housing. Biotechnol. Bioeng. 2009;103: 574–581. © 2009 Wiley Periodicals, Inc.     

Designing filters for fast-known NcRNA identification

Detecting members of known noncoding RNA (ncRNA) families in genomic DNA is an important part of sequence annotation. However, the most widely used tool for modeling ncRNA families, the covariance model (CM), incurs a high-computational cost when used for genome-wide search. This cost can be reduced by using a filter to exclude sequences that are unlikely to contain the ncRNA of interest, applying the CM only where it is likely to match strongly. Despite recent advances, designing an efficient filter that can detect ncRNA instances lacking strong conservation while excluding most irrelevant sequences remains challenging. In this work, we design three types of filters based on multiple secondary structure profiles (SSPs). An SSP augments a regular profile (i.e., a position weight matrix) with secondary structure information but can still be efficiently scanned against long sequences. Multi-SSPbased filters combine evidence from multiple SSP matches and can achieve high sensitivity and specificity. Our SSP-based filters are extensively tested in BRAliBase III data set, Rfam 9.0, and a published soil metagenomic data set. In addition, we compare the SSPbased filters with several other ncRNA search tools including Infernal (with profile HMMs as filters), ERPIN, and tRNAscan-SE. Our experiments demonstrate that carefully designed SSP filters can achieve significant speedup over unfiltered CM search while maintaining high sensitivity for various ncRNA families. The designed filters and filter-scanning programs are available at our website: www.cse.msu.edu/~yannisun/ssp/.     

Ames test: mutagenic activity of airborne particles collected on airconditioner filters during the fire at a Sandoz storehouse in Schweizerhalle on November 1, 1986

The mutagenic activity of methanol extracts from airconditioner filters was tested using the standard plate-incorporation procedure for the Ames test and the strains Salmonella typhimurium TA97, TA98 and TA100 as test organisms. In a first set of experiments filters from 4 buildings were investigated. For each building the mutagenic activity of a filter which was in use during the fire (fire-exposed) was compared with the mutagenic activity of a filter which was exposed for a similar time span to normal urban air (non-exposed). While for 1 pair of filters the non-exposed extract was more mutagenic than the fire-exposed material, the opposite was found for 2 other filter pairs, and in 1 case there was hardly any difference in the mutagenic activities of the fire-exposed and the non-exposed filter extracts. Overall differences by factors up to 100 were observed in the mutants/m3 air values of the most and the least mutagenic filter extracts. The second group of experiments was performed to investigate the variations in mutagenic activity of filter extracts occurring due to changes in the weather conditions. Airborne particles were collected for 3 consecutive periods of 10-11 days at the 2 buildings where the extracts of the fire-exposed filters had been found to be more mutagenic than the corresponding control materials. The differences between the strongest and the weakest mutagenic filter extracts of these series were similar to the differences observed previously between the fire-exposed filters and the non-exposed filter materials. The highest mutagenic activities found in the second group of experiments was similar, at both sites, to the mutagenic activities measured in the fire-exposed extracts from these 2 buildings. Since the differences in the mutagenic activities of filters exposed to urban air during the different meteorological conditions were similar to the differences observed between fire-exposed and non-exposed materials, it is not possible to state whether the fire led to the distribution of mutagenic chemicals, although it is theoretically possible. However, based on the observation that the maximal mutagenic activities of the fire-exposed and the non-exposed extracts were similar, the present study allows the conclusion that the mutagenic burden for the population of the area of Basel was not significantly increased by the fire in Schweizerhalle on November 1, 1986.     

Numerical analysis of the hemodynamics and embolus capture of a greenfield vena cava filter

BACKGROUND: Vena Cava filters are used to prevent pulmonary embolism in patients with deep vein thrombosis who are unresponsive to anticoagulation therapy. Various filter designs exist in the market with different characteristics distinguishing them. An understanding of the characteristics of these filters is desirable in order to develop better designs. METHODS: A computational fluid dynamical study of the flow over an unoccluded stainless steel Greenfield Vena Cava filter (Boston Scientific, Watertown, MA) to determine its properties has been performed. Simulation of flow over a filter placed axisymmetrically in a rounded inferior vena cava has been performed at a Reynolds numbers of 1000 and the consequences of the flow (by studying parameters like shear stress and stagnation zones) have been discussed. Furthermore, a new finite element based numerical method has been developed that allows the study of capturing properties of Inferior Vena Cava filters. The key idea is the introduction of a thin-wire-model (TWM) that enables a drastic reduction in the computational cost while still maintaining control on the physics of the problem. This numerical technique has been applied to evaluate the embolus capture characteristic of a Greenfield filter. RESULTS: The flow around the unoccluded filter is found to be steady and laminar at the conditions studied. A recirculation/stagnation zone develops immediately downstream of the filter head. This zone is significantly larger when the central hole is occluded. The shear stress and stagnation zone properties for such a flow over a Greenfield filter are compared with existing literature (in vitro studies). A graph showing the regions wherein clots escape or get captured has been determined by a means of numerical simulations. The data has further been analyzed to determine the probability of clot capture as function of the clot size. CONCLUSIONS: The stagnation zone formed behind the head of the Greenfield filter is found to be smaller in size when compared to that of the same filter with the central hole occluded. A map of the shear stress distribution shows a small region having the potential for thrombogenesis. The non-Newtonian properties of blood are not seen to cause much variation in the flow field when compared to the Newtonian model. However variation in the cava size leads to a significant change in the shear stresses. This study also establishes a novel method wherein computational means are used to determine the efficacy of clot capturing of filters. These techniques can further be used to compare the different characteristics among filters.     

The Essential Complexity of Auditory Receptive Fields

Encoding properties of sensory neurons are commonly modeled using linear finite impulse response (FIR) filters. For the auditory system, the FIR filter is instantiated in the spectro-temporal receptive field (STRF), often in the framework of the generalized linear model. Despite widespread use of the FIR STRF, numerous formulations for linear filters are possible that require many fewer parameters, potentially permitting more efficient and accurate model estimates. To explore these alternative STRF architectures, we recorded single-unit neural activity from auditory cortex of awake ferrets during presentation of natural sound stimuli. We compared performance of > 1000 linear STRF architectures, evaluating their ability to predict neural responses to a novel natural stimulus. Many were able to outperform the FIR filter. Two basic constraints on the architecture lead to the improved performance: (1) factorization of the STRF matrix into a small number of spectral and temporal filters and (2) low-dimensional parameterization of the factorized filters. The best parameterized model was able to outperform the full FIR filter in both primary and secondary auditory cortex, despite requiring fewer than 30 parameters, about 10% of the number required by the FIR filter. After accounting for noise from finite data sampling, these STRFs were able to explain an average of 40% of A1 response variance. The simpler models permitted more straightforward interpretation of sensory tuning properties. They also showed greater benefit from incorporating nonlinear terms, such as short term plasticity, that provide theoretical advances over the linear model. Architectures that minimize parameter count while maintaining maximum predictive power provide insight into the essential degrees of freedom governing auditory cortical function. They also maximize statistical power available for characterizing additional nonlinear properties that limit current auditory models.     

Reducing false-positive prediction of minimotifs with a genetic interaction filter

Background

Minimotifs are short contiguous peptide sequences in proteins that have known functions. At its simplest level, the minimotif sequence is present in a source protein and has an activity relationship with a target, most of which are proteins. While many scientists routinely investigate new minimotif functions in proteins, the major web-based discovery tools have a high rate of false-positive prediction. Any new approach that reduces false-positives will be of great help to biologists.

Methods and Findings

We have built three filters that use genetic interactions to reduce false-positive minimotif predictions. The basic filter identifies those minimotifs where the source/target protein pairs have a known genetic interaction. The HomoloGene genetic interaction filter extends these predictions to predicted genetic interactions of orthologous proteins and the node-based filter identifies those minimotifs where proteins that have a genetic interaction with the source or target have a genetic interaction. Each filter was evaluated with a test data set containing thousands of true and false-positives. Based on sensitivity and selectivity performance metrics, the basic filter had the best discrimination for true positives, whereas the node-based filter had the highest sensitivity. We have implemented these genetic interaction filters on the Minimotif Miner 2.3 website. The genetic interaction filter is particularly useful for improving predictions of posttranslational modifications such as phosphorylation and proteolytic cleavage sites.

Conclusions

Genetic interaction data sets can be used to reduce false-positive minimotif predictions. Minimotif prediction in known genetic interactions can help to refine the mechanisms behind the functional connection between genes revealed by genetic experimentation and screens.     

MMPI Drug-Eluting IVC Filter Decreases Adhesion Between Caval Wall and Filter

The implantation of inferior vena cava (IVC) filter was a safe and effective therapy for preventing fatal pulmonary embolism. However, there are risks associated with long-term implantation of filters. Retrievable filters are designed to be removed, but may also remain permanently. Retrieval can reduce risk of long-term complications. The difficulty or impossibility of retrieval is still an issue of retrieval filter. The major causes of filters retrieval failure were intimal overgrowth and severely tilted filter with apex embedded into the caval wall. Matrix metalloproteinases (MMPs) play a key role in neointimal hyperplasia. It is documented that neointimal hyperplasia can be reduced by inhibiting MMP activity and hence smooth muscle cell migration. MMP inhibitors (MMPI) can potently inhibit the activity of MMPs. We hypothesize that a drug-eluting filter which contains MMPI may inhibit IVC neointimal hyperplasia and decrease the adhesion between vascular wall and filter struts. After implantation of drug-eluting retrieval filter, MMPI is released slowly at the sites where the filter struts are in contact with the caval wall; the activity of MMPs of caval wall will be inhibited, injury in basement membrane is decreased, migration of SMC maybe reduced, and the release of extracellular matrix maybe lessened. Finally, neointimal hyperplasia maybe inhibited, the adhesion between vascular wall and filter maybe weakened, the success rate maybe increased, and the vascular injury during retrieval maybe reduced. The hypothesis might improve the long-term prognosis of venous thromboembolism patients.     

An oxygen electrode-based assay of catalase activity as a rapid method for estimating the bacterial content of foods

An oxygen electrode-based assay of catalase was developed as a simple method of assessing contamination by bacteria capable of respiration. The method gave a rapid and reasonable quantification of cell numbers in pure cultures and was able to detect 10³ bacteria/ml in some cases. The sensitivity of the method was dependent on the identity of the culture and when applied to foods the sensitivity was reduced due to the presence of non-microbial catalase. The use of electropositively charged filters to remove the organisms from the food sample improved the sensitivity and the relationship between catalase activity and cell numbers in some foods.     

Evaluation of Pfizer selective enterococcus and KF media for recovery of fecal streptococci from water by membrane filtration.

Pfizer selective enterococcus (PSE) and KF agars were compared for their recovery of fecal streptococci from sewage effluent on membrane filters. The results showed that PSE agar is highly selective for the enterococci. The tan color resulting from esculin hydrolysis, which was not always visible on the surfaces of the colonies, is not considered a necessary differential characteristic on PSE agar since more than 90% of all colonies recovered on membrane filters were confirmed as fecal streptococci and 86% were confirmed as enterococci. The detection of esculin hydrolysis on membrane filters was not improved by using the new Millipore type HC filter. KF agar recovered significantly greater numbers of organisms but was not as selective, with 83% of the typical colonies being confirmed as fecal streptococci and 54% as enterococci. An attempt to improve the selectivity of KF agar while retaining its inclusiveness by incubation at 45 C was not successful.     

Optimal use of conservation and accessibility filters in microRNA target prediction

It is generally accepted that filtering microRNA (miRNA) target predictions by conservation or by accessibility can reduce the false discovery rate. However, these two strategies are usually not exploited in a combined and flexible manner. Here, we introduce PACCMIT, a flexible method that filters miRNA binding sites by their conservation, accessibility, or both. The improvement in performance obtained with each of these three filters is demonstrated on the prediction of targets for both i) highly and ii) weakly conserved miRNAs, i.e., in two scenarios in which the miRNA-target interactions are subjected to different evolutionary pressures. We show that in the first scenario conservation is a better filter than accessibility (as both sensitivity and precision are higher among the top predictions) and that the combined filter improves performance of PACCMIT even further. In the second scenario, on the other hand, the accessibility filter performs better than both the conservation and combined filters, suggesting that the site conservation is not equally effective in rejecting false positive predictions for all miRNAs. Regarding the quality of the ranking criterion proposed by Robins and Press and used in PACCMIT, it is shown that top ranking interactions correspond to more downregulated proteins than do the lower ranking interactions. Comparison with several other target prediction algorithms shows that the ranking of predictions provided by PACCMIT is at least as good as the ranking generated by other conservation-based methods and considerably better than the energy-based ranking used in other accessibility-based methods.     

Efficacy of antimicrobial filter treatments on microbial colonization of air panel filters

AIMS: To assess the activity of biostatic agents on the microbial colonization of panel filters. METHODS AND RESULTS: Microfibre glass acrylic filters, both used and unused, were examined for the presence of microorganisms. Test strains were used to verify microbial colonization of filter media. Antimicrobial agents were applied to the filter media and tested for their ability to reduce microbial colonization. The integrity of the panel filters and the antimicrobial activity trends of the filter media treated with antimicrobials were verified. A filtration efficiency test was carried out on the treated filters to evaluate filtration performance. Filters treated with antimicrobials demonstrated markedly less microbial colonization (density and varieties of species), higher filtration efficiency and delayed deterioration of the filter. CONCLUSIONS: The most important results of this study are the demonstration of preservation of the integrity of the filters and the lower release of microorganisms from treated filters. SIGNIFICANCE AND IMPACT OF THE STUDY: These results contribute to the resolution of problems concerning the microbial contamination of panel filters in the heating, ventilating and air-conditioning systems commonly used in the electronic industry, pharmaceutical industry, hospitals and other environments where the absence of contaminating particles and microorganisms is required.     

The effect of different high-pass filter settings on peak latencies in the event-related potentials of schizophrenics,patients with Parkinson's disease and controls

Eighteen schizophrenic patients, 16 patients with idiopathic Parkinson's disease, and the same numbers of age, sex and education matched controls were examined with oddball experiments for the generation of P3. Individual averages were high-pass filtered at different cut-off frequencies with single-pole digital filters with equivalent analogue Butterworth filter profiles. The purpose of this procedure was to simulate analogue high-pass filters used in clinical studies from different centres and to examine their potential effect on group differences. Increasing high-pass filters resulted in a phase lead for all peaks examined (N1, P2, N2, P3). The only group differences were found for P3, which showed a greater phase lead in controls than in the patient groups, usually resulting in a more pronounced group difference. Similar wave forms and filter properties could be modelled by synthetic wave forms consisting of sine waves of different frequencies.     

Multilayer immobilized-enzyme filter reactors: urease bound to nylon fabric filters.

Urease was bound to commercially available nonwoven nylon fabric filters. Multilayer immobilized-enzyme filter reactors were constructed by packing varying numbers of urease-nylon filters in a column. Owing to the relatively open structure and high mechanical strength of the filter fabric, compaction and pressure drop effects were minimal. The reactors could be operated in a wide range of substrate concentrations and flow rates under conditions where mass-transfer limitations could be neglected. The kinetic behavior of the immobilized-enzyme filter reactors could be described by a linear form of the integrated Michaelis-Menten equation using a model based on the sequential action of the enzyme filters.     

A colorimetric method for the determination of submicrogram quantities of protein

A simple procedure for the measurement of submicrogram quantities of protein is described which can be used without interference from most common reagents. Protein-containing solutions are spotted on glass fiber filters, washed with trichloroacetic acid, and stained with Coomassie blue. The filters are destained, and the protein-bound colorant is eluted and measured in a spectrophotometer at 590 nm. The response is linear to 5 μg of protein per filter, and as little as 0.1 μg per filter can be accurately determined.     

Comparative analysis of the clastogenicity and cytotoxicity of airborne particulate matter generated during the fire at Schweizerhalle on November 1, 1986

Methanol extracts from 4 pairs of airconditioner filters (one fire-exposed and one control) from various locations (A, B, C and D) at various distances from the site of the fire were examined for their capacity to induce structural chromosomal aberrations and/or cytotoxicity in Chinese hamster V79 cells. Extracts from 2 additional sets of 3 filters which were exposed to urban air for 3 consecutive periods of 10 or 11 days some 4 months after the fire were also tested. Chromosomal aberrations were induced by all filter extracts from location B, as well as by an unused (non-exposed) filter, in a dose-dependent manner. Without the addition of metabolizing enzymes, aberrations were induced only at concentrations which caused more than 95% cell killing. This was not taken as an indication for clastogenic activity of the filter extracts, but was assumed to represent the chromosomal expression of metabolic changes in dying cells. Upon the addition of S9, chromosomal aberrations were induced at biologically relevant survival rates. Under metabolizing conditions, the ranking of the potential of the filter extracts from location B to induce chromosomal aberrations and to cause cell killing was identical. The remaining extracts (locations A, C and D) were therefore tested for cytotoxicity only. The toxicity data indicated that, of 3 pairs of filters, the fire-exposed one was not different from the control. Of the fourth pair (location B), the fire-exposed filter was 2.0-2.5 times more cytotoxic and clastogenic than the control. However, extracts of urban air-exposed filters from this location (exposed in March and April 1987) showed a large variation in toxicity and clastogenicity as well. One was clearly more active than the control (but less than the fire-exposed filter), while the other 2 were either somewhat more or less clastogenic than the control filter. In addition, 4 out of 5 filters from this location were more polluted (as indicated by cytotoxicity) than all the filters from the other locations, irrespective of whether they were fire-exposed or not. It is concluded that the results of this V79 cytotoxicity/clastogenicity test did not confirm the hypothesis that the fire at Schweizerhalle produced clastogenic material at quantities detectable under the conditions employed.     

Picoplankton size distributions in marine and fresh waters: problems with filter fractionation studies

Abstract The retention of algal picoplankton by Nuclepore polycarbonate filters of 0.2, 1.0, 2.0 and 3.0 μm pore size was tested in 2 marine and 3 freshwater sites. When 1 μm Nuclepore filters were used, the percentage of the total cyanobacterial cells passing the filter varied between sites and with increasing depth within sites. As much as 99% of the Synechococcus -like cells was retained by a 1 μm filter. This could lead to an underestimation of the picoplanktonic contribution or, more seriously, an apparent distribution pattern that is an artifact of the choice of filter pore size. Filter retention was also dependent on vaccum pressure during filtration. This study emphasizes the need for direct observation of picoplankton numbers in filter fractionation studies.     

Croatian bibliometric analysis, 2000-2007

To develop search filters and retrieve information estimating the Croatian scientific output (SO) focusing on Public Health (PH) and Preventive Medicine (PM) in MEDLINE. A PubMed search of the MEDLINE database was performed to retrieve articles added to this database between 2000 and 2007. Search filters inspired by previous strategies were applied involving 'geographical', 'place of publication', 'subject' and 'language of publication' aspects. An evaluation of the geographical filter performance was done and sensitivity and specificity were calculated. There were obtained publications in several languages, originated in Croatia, published in Croatia and/or abroad. The Croatian SO in the field of PH-PM was obtained for the same period of time by combining search filters. The evaluation of the filter performance showed sensitivity 95.56% and specificity 100%. The filters constructed permitted the retrieval of the Croatian eight years research output. Increased tendency was observed in the global SO evolution and in the PH-PM area as well. The main languages of publication were English and Croatian. This study is a contribution to research in the field of scientific documentation and further analysis is recommended in constructing and developing search filters to retrieve and focus on specific information.     

On the Pharyngeal Feeding Filter of the Salp Pegea confoederata (Tunicata: Thaliacea)

In Pegea, scanning electron microscopy of what appear to be the least damaged portions of the filter shows that it has a regular rectangular mesh consisting of thick (100 nm) fibres at right angles to thinner (50 nm) fibres. The rectangular pores of the filter are around 3.3 × 0.57 μm. These measured values from filters that have suffered shrinkage (to an uncertain degree) during preparation are considered to indicate that the actual pore size in life is some 4.0 × 0.7 μm. The mucous-net feeding filter of salps differs from that of other tunicates since flow through it results from muscular activity. Calculations based on the estimated pore size and filtering rate suggest that during part of the filtering cycle, the pressure drop across the filter is considerably greater than that across other tunicate mucous-net filters.     

Detection of virus in water: sensitivity of the tentative standard method for drinking water.

The sensitivity of several microporous virus-adsorbent media for reliably detecting low levels of poliovirus from 380 and 1,900 liters of drinking water by use of the tentative standard method was investigated. The virus-adsorbent media tested were (i) nitrocellulose membrane filters, (ii) epoxy-fiber glass-asbestos filters, (iii) yarn-wound fiber glass depth filters, and (iv) epoxy-fiber glass filter tubes. Virus was adsorbed to the filter media at pH 3.5 and eluted with glycine buffer, pH 11.5. The results from 44 samples demonstrated that poliovirus was detected with a 95% reliability at mean virus input levels of 3 to 7 plaque-forming units/380 liters when 1,900 liters of water was sampled. At mean virus input levels of less than 1 to 2 plaque-forming units/380 liters, the detection reliability was 66% in 76 samples when 1,900 liters of water was sampled. No significant difference in virus detection sensitivity was observed among the various virus adsorbent media tested. Overall virus recovery efficiency ranged from 28 to 42%, with a grand average of 35%. Members of the coxsackievirus groups A and B, echovirus, and adenovirus were also detected when 380 and 1,900 liters of water were sampled. These experimental observations attest to the sensitivity of the tentative standard method for detecting low levels of virus in large volumes of drinking water.