Fast local fragment chaining using sum-of-pair gap costs

<p>Abstract</p> <p>Background</p> <p>Fast seed-based alignment heuristics such as <monospace>BLAST</monospace> and <monospace>BLAT</monospace> have become indispensable tools in comparative genomics for all studies aiming at the evolutionary relations of proteins, genes, and non-coding RNAs. This is true in particular for the large mammalian genomes. The sensitivity and specificity of these tools, however, crucially depend on parameters such as seed sizes or maximum expectation values. In settings that require high sensitivity the amount of short local match fragments easily becomes intractable. Then, fragment chaining is a powerful leverage to quickly connect, score, and rank the fragments to improve the specificity.</p> <p>Results</p> <p>Here we present a fast and flexible fragment chainer that for the first time also supports a sum-of-pair gap cost model. This model has proven to achieve a higher accuracy and sensitivity in its own field of application. Due to a highly time-efficient index structure our method outperforms the only existing tool for fragment chaining under the linear gap cost model. It can easily be applied to the output generated by alignment tools such as <monospace>segemehl</monospace> or <monospace>BLAST</monospace>. As an example we consider homology-based searches for human and mouse snoRNAs demonstrating that a highly sensitive <monospace>BLAST</monospace> search with subsequent chaining is an attractive option. The sum-of-pair gap costs provide a substantial advantage is this context.</p> <p>Conclusions</p> <p>Chaining of short match fragments helps to quickly and accurately identify regions of homology that may not be found using local alignment heuristics alone. By providing both the linear and the sum-of-pair gap cost model, a wider range of application can be covered. The software clasp is available at <url>http://www.bioinf.uni-leipzig.de/Software/clasp/</url>.</p

Dielectrophoretic immobilisation of antibodies on microelectrode arrays

A silicon based chip device with a regular array of more than 100 000 cylindrical sub-microelectrodes has been developed for the dielectrophoretic (DEP) manipulation of nanoparticles and molecules in solution. It was fabricated by a standard CMOS (complementary metal oxide semiconductor) compatible process. The distribution of the electrical field gradient was calculated to predict the applicability of the setup. Heating due to field application was determined microscopically using a temperature sensitive fluorescent dye. Depending on voltage and frequency, temperature increase was found to be compatible with protein function. Successful field controlled immobilisation of biomolecules from solution was demonstrated with the autofluorescent protein R-phycoerythrin (RPE) and with fluorescently labelled IgG antibodies. Biological activity after DEP application was proven by immobilisation of an anti-RPE antibody and subsequent binding of RPE. These results demonstrate that the developed chip system allows the directed immobilisation of proteins onto microelectrodes by dielectrophoresis without the need for any chemical modification and that protein function is preserved. Being based on standard lithographical methods, further miniaturisation and on-chip integration of electronics towards a multiparameter single cell analysis system appear near at hand

Dielectrophoretic immobilisation of antibodies on microelectrode arrays

A silicon based chip device with a regular array of more than 100 000 cylindrical sub-microelectrodes has been developed for the dielectrophoretic (DEP) manipulation of nanoparticles and molecules in solution. It was fabricated by a standard CMOS (complementary metal oxide semiconductor) compatible process. The distribution of the electrical field gradient was calculated to predict the applicability of the setup. Heating due to field application was determined microscopically using a temperature sensitive fluorescent dye. Depending on voltage and frequency, temperature increase was found to be compatible with protein function. Successful field controlled immobilisation of biomolecules from solution was demonstrated with the autofluorescent protein R-phycoerythrin (RPE) and with fluorescently labelled IgG antibodies. Biological activity after DEP application was proven by immobilisation of an anti-RPE antibody and subsequent binding of RPE. These results demonstrate that the developed chip system allows the directed immobilisation of proteins onto microelectrodes by dielectrophoresis without the need for any chemical modification and that protein function is preserved. Being based on standard lithographical methods, further miniaturisation and on-chip integration of electronics towards a multiparameter single cell analysis system appear near at hand

A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection

Numerous high-throughput sequencing studies have focused on detecting conventionally spliced mRNAs in RNA-seq data. However, non-standard RNAs arising through gene fusion, circularization or trans-splicing are often neglected. We introduce a novel, unbiased algorithm to detect splice junctions from single-end cDNA sequences. In contrast to other methods, our approach accommodates multi-junction structures. Our method compares favorably with competing tools for conventionally spliced mRNAs and, with a gain of up to 40% of recall, systematically outperforms them on reads with multiple splits, trans-splicing and circular products

Loops under Strategies ... Continued

While there are many approaches for automatically proving termination of term rewrite systems, up to now there exist only few techniques to disprove their termination automatically. Almost all of these techniques try to find loops, where the existence of a loop implies non-termination of the rewrite system. However, most programming languages use specific evaluation strategies, whereas loop detection techniques usually do not take strategies into account. So even if a rewrite system has a loop, it may still be terminating under certain strategies. Therefore, our goal is to develop decision procedures which can determine whether a given loop is also a loop under the respective evaluation strategy. In earlier work, such procedures were presented for the strategies of innermost, outermost, and context-sensitive evaluation. In the current paper, we build upon this work and develop such decision procedures for important strategies like leftmost-innermost, leftmost-outermost, (max-)parallel-innermost, (max-)parallel-outermost, and forbidden patterns (which generalize innermost, outermost, and context-sensitive strategies). In this way, we obtain the first approach to disprove termination under these strategies automatically.Comment: In Proceedings IWS 2010, arXiv:1012.533

Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0