DNA watermarks: A proof of concept

<p>Abstract</p> <p>Background</p> <p>DNA-based watermarks are helpful tools to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. <it>In silico </it>analyses showed that in coding regions synonymous codons can be used to insert encrypted information into the genome of living organisms by using the DNA-Crypt algorithm.</p> <p>Results</p> <p>We integrated an authenticating watermark in the Vam7 sequence. For our investigations we used a mutant <it>Saccharomyces cerevisiae </it>strain, called CG783, which has an amber mutation within the Vam7 sequence. The CG783 cells are unable to sporulate and in addition display an abnormal vacuolar morphology. Transformation of CG783 with pRS314 Vam7 leads to a phenotype very similar to the wildtype yeast strain CG781. The integrated watermark did not influence the function of Vam7 and the resulting phenotype of the CG783 cells transformed with pRS314 Vam7-TB shows no significant differences compared to the CG783 cells transformed with pRS314 Vam7.</p> <p>Conclusion</p> <p>From our experiments we conclude that the DNA watermarks produced by DNA-Crypt do not influence the translation from mRNA into protein. By analyzing the vacuolar morphology, growth rate and ability to sporulate we confirmed that the resulting Vam7 protein was functionally active.</p

DNA watermarks in non-coding regulatory sequences

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Interactive polar diagrams for model comparison

Objective Evaluating the performance of multiple complex models, such as those found in biology, medicine, climatology, and machine learning, using conventional approaches is often challenging when using various evaluation metrics simultaneously. The traditional approach, which relies on presenting multi-model evaluation scores in the table, presents an obstacle when determining the similarities between the models and the order of performance. Methods By combining statistics, information theory, and data visualization, juxtaposed Taylor and Mutual Information Diagrams permit users to track and summarize the performance of one model or a collection of different models. To uncover linear and nonlinear relationships between models, users may visualize one or both charts. Results Our library presents the first publicly available implementation of the Mutual Information Diagram and its new interactive capabilities, as well as the first publicly available implementation of an interactive Taylor Diagram. Extensions have been implemented so that both diagrams can display temporality, multimodality, and multivariate data sets, and feature one scalar model property such as uncertainty. Our library, named polar-diagrams, supports both continuous and categorical attributes. Conclusion The library can be used to quickly and easily assess the performances of complex models, such as those found in machine learning, climate, or biomedical domains

Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism

Deep sequencing is able to generate a complete picture of the retroviral quasi-species in a patient. We demonstrate that the unprecedented power of deep sequencing in conjunction with computational data analysis has great potential for clinical diagnostics and basic research. Specifically, we analyzed longitudinal deep sequencing data from patients in a study with Vicriviroc, a drug that blocks the HIV-1 co-receptor CCR5. Sequences covered the V3-loop of gp120, known to be the main determinant of co-receptor tropism. First, we evaluated this data with a computational model for the interpretation of V3-sequences with respect to tropism, and we found complete agreement with results from phenotypic assays. Thus, the method could be applied in cases where phenotypic assays fail. Second, computational analysis led to the discovery of a characteristic pattern in the quasi-species that foreshadows switches of co-receptor tropism. This analysis could help to unravel the mechanism of tropism switches, and to predict these switches weeks to months before they can be detected by a phenotypic assay

Analyse von Ursachen und Co-Faktoren bei frustraner mechanischer Rekanalisation beim ischämischen Schlaganfall

In der vorliegenden Studie wurden die Ursachen der frustranen Thrombektomie bei Patienten mit akutem ischämischem Schlaganfall des vorderen Stromgebietes (A. carotis interna, A. cerebri media) untersucht. Die gesamte Studienpopulation umfasste 100 gescheiterte Interventionen und 100 zufällig ausgewählte Kontrollpatienten aus einer Gesamtheit von 596 am Universitätsklinikum des Saarlandes im Zeitraum Januar 2014 bis Oktober 2018 interventionell therapierten Patienten. Das Kollektiv der beiden Gruppen unterschied sich statistisch nicht in Alter, Geschlecht und der Symptomausprägung. Als erfolgreiche Intervention wurde ein postinterventioneller TICI-Score von 2b oder höher definiert. Es zeigte sich, dass das neurovaskuläre Zentrum in Homburg im Vergleich zur internationalen Literatur vergleichbare Erfolgsraten von etwa 83,2% aufweist. In der Studienpopulation erhöht die intravenöse Lysetherapie vor Intervention die Erfolgsrate signifikant. Außerdem ergab sich ein statistischer Zusammenhang zwischen der dauerhaften Einnahme von Nitraten und einer erfolgreichen Intervention. 20% der gescheiterten Interventionen sind auf technisch mechanische Hindernisse zurückzuführen. Beispielsweise war dabei kein arterieller Zugang zu etablieren oder die Verschlussstelle konnte aufgrund von Stenosen oder Elongationen nicht erreicht werden. In dieser Gruppe konnte eine deutliche Häufung von pAVK und der Einnahme von Acetylsalicylsäure dargelegt werden. Des Weiteren traten bei diesen Patienten technisch-mechanische Hindernisse häufiger bei Verschlüssen der A. carotis interna und seltener in der A. cerebri media, Segment M1 auf. Bei 80% der frustranen Thrombektomien gelang es zwar, den Verschluss zu erreichen, allerdings konnte das Gefäß aus anderen Gründen nicht oder nicht vollständig eröffnet werden. Vorhofflimmern trat bei diesen Patienten seltener auf als in der Kontrollgruppe. Eine Gerinnungsstörung liegt dagegen signifikant häufiger vor. Hinsichtlich der Gerinnungstherapie mit Cumarinen oder Direkten Oralen Antikoagulantien zeigte sich in keiner der Gruppen ein Unterschied. Auch Laborparameter für eine Entzündungsreaktion und die Gerinnung waren in beiden Gruppen vergleichbar. Zeitliche Faktoren bezogen auf Symptombeginn, Lyse und Intervention scheinen für den Rekanalisationserfolg keine Rolle zu spielen, obwohl aus der Literatur bekannt ist, dass sie das Outcome des Patienten stark beeinflussen. Histologische Untersuchungen gewonnener Thromben zeigten – bei einer Fallzahl von nur 6 Proben – keine Differenzen, ebenso wenig wie CT-morphologische Charakteristika des Thrombus. Zusammenfassend lässt sich feststellen, dass etwa 17% aller geplanten Interventionen nach obiger Definition frustran verlaufen. Bei 20% davon, liegt die Ursache in technisch-mechanischen Hindernissen und eine direkte Punktion der Carotiden könnte in einigen Fällen Abhilfe schaffen, um die Verschlussstelle zu erreichen. Bei den übrigen 80% der scheiternden Interventionen liegt die Ursache hauptsächlich in zwei Gründen: Entweder kann trotz erfolgreicher Platzierung des Stent-Retrievers kein Gerinnsel geborgen werden oder es bleibt ein Verschluss distal gelegener Gefäßäste bestehen. Komplikationen, wie Dissektionen und subarachnoidale Blutungen, sind insgesamt selten. Anzumerken ist, dass nur angiographische Daten und keine klinischen Parameter betreffend das Outcome erhoben wurden. Mit 200 Patienten war die untersuchte Fallzahl nicht sehr groß, sodass keine statistische Signifikanz erreicht werden konnte und sich bei vielen Parametern lediglich Tendenzen erkennen lassen. Eine Ausweitung der Studie auf andere Zentren oder eine Wiederholung zu einem späteren Zeitpunkt mit einer größeren Patientenzahl wäre daher wünschenswert.The present study investigated the causes of failing thrombectomy in patients with acute ischemic stroke of the anterior circulation (A. carotis interna, A. cerebri media). The entire study population comprised 100 failed interventions and 100 randomly selected control patients from a total of 596 interventionally treated patients at Saarland University Hospital between January 2014 and October 2018. The collective of the two groups did not differ statistically in age, sex and symptom severity. A postinterventional TICI score of 2b or higher was defined as a successful intervention. It was found that the neurovascular center in Homburg had comparable success rates to the international literature of about 83.2%. In the study population, intravenous thrombolysis before intervention significantly increases the success rate. Furthermore, there was a statistical correlation between the long-term intake of nitrates and a successful intervention. 20% of the failing interventions are due to technical mechanical obstacles. For example, no arterial access could be established, or the occlusion site could not be reached due to stenosis or elongation. In this group, an association with PAOD and the intake of acetylsalicylic acid could be demonstrated. In addition, technical and mechanical obstacles occurred more frequently in occlusions of the internal carotid artery and less frequently in the cerebral media artery, segment M1. In 80% of the frustrated thrombectomies it was possible to reach the occlusion site, but for other reasons the vessel could not or not completely be recanalized. In this group, atrial fibrillation is less frequent than in the control group. In addition, patients with a coagulation disorder have a significantly worse result. Regarding coagulation therapy with coumarins or direct oral anticoagulants, there was no difference in any of the groups. Laboratory parameters for inflammatory response and coagulation were also comparable in both groups. Time factors related to symptom onset, lysis and intervention do not seem to play a role in the success of recanalization, although it is known from the literature that they strongly influence the outcome of the patient. Histological examinations of thrombi obtained - with a case number of only 6 samples - showed no differences, nor did CT-morphological data of the thrombus. In summary, 17% of all interventions fail according to the definition above. In 20% of these, there are technical reasons for failure. Direct carotid puncture could be a solution to reach the occlusion site. In the remainig 80% there are two main causes for failure: On the one hand, no thrombus material can be extracted although the stent-retriever-device is correctly in place and on the other hand, distal vessel branches stay occluded. In total, complications such as subarachnoid hemorrhage or iatrogenic dissection are rare. It should be noted that only angiographic data and no clinical parameters concerning patient outcome were collected. With 200 patients, the investigated case number was not very large, so that no statistic significance could be proven and only tendencies can be identified for many parameters. An extension of the study to other centers or a repetition with a larger number of patients would therefore be necessary

Insights into the classification of small GTPases

In this study we used a Random Forest-based approach for an assignment of small guanosine triphosphate proteins (GTPases) to specific subgroups. Small GTPases represent an important functional group of proteins that serve as molecular switches in a wide range of fundamental cellular processes, including intracellular transport, movement and signaling events. These proteins have further gained a special emphasis in cancer research, because within the last decades a huge variety of small GTPases from different subgroups could be related to the development of all types of tumors. Using a random forest approach, we were able to identify the most important amino acid positions for the classification process within the small GTPases superfamily and its subgroups. These positions are in line with the results of earlier studies and have been shown to be the essential elements for the different functionalities of the GTPase families. Furthermore, we provide an accurate and reliable software tool (GTPasePred) to identify potential novel GTPases and demonstrate its application to genome sequences

Exploiting HIV-1 protease and reverse transcriptase cross-resistance information for improved drug resistance prediction by means of multi-label classification

Gini impurity PIs. (PDF 8 kb

FRI -- Feature Relevance Intervals for Interpretable and Interactive Data Exploration

Most existing feature selection methods are insufficient for analytic purposes as soon as high dimensional data or redundant sensor signals are dealt with since features can be selected due to spurious effects or correlations rather than causal effects. To support the finding of causal features in biomedical experiments, we hereby present FRI, an open source Python library that can be used to identify all-relevant variables in linear classification and (ordinal) regression problems. Using the recently proposed feature relevance method, FRI is able to provide the base for further general experimentation or in specific can facilitate the search for alternative biomarkers. It can be used in an interactive context, by providing model manipulation and visualization methods, or in a batch process as a filter method.Comment: Addition of IEEE copyright notice. Accepted for CIBCB 2019 (https://cibcb2019.icas.xyz/

MOSGA: Modular Open-Source Genome Annotator

The generation of high-quality assemblies, even for large eukaryotic genomes, has become a routine task for many biologists thanks to recent advances in sequencing technologies. However, the annotation of these assemblies - a crucial step towards unlocking the biology of the organism of interest - has remained a complex challenge that often requires advanced bioinformatics expertise. Here we present MOSGA, a genome annotation framework for eukaryotic genomes with a user-friendly web-interface that generates and integrates annotations from various tools. The aggregated results can be analyzed with a fully integrated genome browser and are provided in a format ready for submission to NCBI. MOSGA is built on a portable, customizable, and easily extendible Snakemake backend, and thus, can be tailored to a wide range of users and projects. We provide MOSGA as a publicly free available web service at https://mosga.mathematik.uni-marburg.de and as a docker container at registry.gitlab.com/mosga/mosga:latest. Source code can be found at https://gitlab.com/mosga/mosg