Algebraic correction methods for computational assessment of clone overlaps in DNA fingerprint mapping

<p>Abstract</p> <p>Background</p> <p>The Sulston score is a well-established, though approximate metric for probabilistically evaluating postulated clone overlaps in DNA fingerprint mapping. It is known to systematically over-predict match probabilities by various orders of magnitude, depending upon project-specific parameters. Although the exact probability distribution is also available for the comparison problem, it is rather difficult to compute and cannot be used directly in most cases. A methodology providing both improved accuracy and computational economy is required.</p> <p>Results</p> <p>We propose a straightforward algebraic correction procedure, which takes the Sulston score as a provisional value and applies a power-law equation to obtain an improved result. Numerical comparisons indicate dramatically increased accuracy over the range of parameters typical of traditional agarose fingerprint mapping. Issues with extrapolating the method into parameter ranges characteristic of newer capillary electrophoresis-based projects are also discussed.</p> <p>Conclusion</p> <p>Although only marginally more expensive to compute than the raw Sulston score, the correction provides a vastly improved probabilistic description of hypothesized clone overlaps. This will clearly be important in overlap assessment and perhaps for other tasks as well, for example in using the ranking of overlap probabilities to assist in clone ordering.</p

Statistical aspects of discerning indel-type structural variation via DNA sequence alignment

<p>Abstract</p> <p>Background</p> <p>Structural variations in the form of DNA insertions and deletions are an important aspect of human genetics and especially relevant to medical disorders. Investigations have shown that such events can be detected via tell-tale discrepancies in the aligned lengths of paired-end DNA sequencing reads. Quantitative aspects underlying this method remain poorly understood, despite its importance and conceptual simplicity. We report the statistical theory characterizing the length-discrepancy scheme for Gaussian libraries, including coverage-related effects that preceding models are unable to account for.</p> <p>Results</p> <p>Deletion and insertion statistics both depend heavily on physical coverage, but otherwise differ dramatically, refuting a commonly held doctrine of symmetry. Specifically, coverage restrictions render insertions much more difficult to capture. Increased read length has the counterintuitive effect of worsening insertion detection characteristics of short inserts. Variance in library insert length is also a critical factor here and should be minimized to the greatest degree possible. Conversely, no significant improvement would be realized in lowering fosmid variances beyond current levels. Detection power is examined under a straightforward alternative hypothesis and found to be generally acceptable. We also consider the proposition of characterizing variation over the entire spectrum of variant sizes under constant risk of false-positive errors. At 1% risk, many designs will leave a significant gap in the 100 to 200 bp neighborhood, requiring unacceptably high redundancies to compensate. We show that a few modifications largely close this gap and we give a few examples of feasible spectrum-covering designs.</p> <p>Conclusion</p> <p>The theory resolves several outstanding issues and furnishes a general methodology for designing future projects from the standpoint of a spectrum-wide constant risk.</p

The theory of discovering rare variants via DNA sequencing

<p>Abstract</p> <p>Background</p> <p>Rare population variants are known to have important biomedical implications, but their systematic discovery has only recently been enabled by advances in DNA sequencing. The design process of a discovery project remains formidable, being limited to <it>ad hoc </it>mixtures of extensive computer simulation and pilot sequencing. Here, the task is examined from a general mathematical perspective.</p> <p>Results</p> <p>We pose and solve the population sequencing design problem and subsequently apply standard optimization techniques that maximize the discovery probability. Emphasis is placed on cases whose discovery thresholds place them within reach of current technologies. We find that parameter values characteristic of rare-variant projects lead to a general, yet remarkably simple set of optimization rules. Specifically, optimal processing occurs at constant values of the per-sample redundancy, refuting current notions that sample size should be selected outright. Optimal project-wide redundancy and sample size are then shown to be inversely proportional to the desired variant frequency. A second family of constants governs these relationships, permitting one to immediately establish the most efficient settings for a given set of discovery conditions. Our results largely concur with the empirical design of the Thousand Genomes Project, though they furnish some additional refinement.</p> <p>Conclusion</p> <p>The optimization principles reported here dramatically simplify the design process and should be broadly useful as rare-variant projects become both more important and routine in the future.</p

Extension of Lander-Waterman theory for sequencing filtered DNA libraries

BACKGROUND: The degree to which conventional DNA sequencing techniques will be successful for highly repetitive genomes is unclear. Investigators are therefore considering various filtering methods to select against high-copy sequence in DNA clone libraries. The standard model for random sequencing, Lander-Waterman theory, does not account for two important issues in such libraries, discontinuities and position-based sampling biases (the so-called "edge effect"). We report an extension of the theory for analyzing such configurations. RESULTS: The edge effect cannot be neglected in most cases. Specifically, rates of coverage and gap reduction are appreciably lower than those for conventional libraries, as predicted by standard theory. Performance decreases as read length increases relative to island size. Although opposite of what happens in a conventional library, this apparent paradox is readily explained in terms of the edge effect. The model agrees well with prototype gene-tagging experiments for Zea mays and Sorghum bicolor. Moreover, the associated density function suggests well-defined probabilistic milestones for the number of reads necessary to capture a given fraction of the gene space. An exception for applying standard theory arises if sequence redundancy is less than about 1-fold. Here, evolution of the random quantities is independent of library gaps and edge effects. This observation effectively validates the practice of using standard theory to estimate the genic enrichment of a library based on light shotgun sequencing. CONCLUSION: Coverage performance using a filtered library is significantly lower than that for an equivalent-sized conventional library, suggesting that directed methods may be more critical for the former. The proposed model should be useful for analyzing future projects

Selbstentzauberung einer Avantgarde

Among German economist a heavy struggle about economic policy and the role of the ECB is going on. In this quarrel some more traditional Marxists come rather close to neoliberal positions which shows a certain theoretical lack of traditional Marxism in the field of value and money theory

Lokalisierung von Störlichtbögen im Photovoltaiksystem

Ziel der Forschungsarbeit ist die Beschreibung neuartiger Methoden zur Lokalisierung von Störlichtbögen in Photovoltaikanlagen. Dafür wird systematisch die Brennspannung von Gleichstrom-Lichtbögen im Frequenzbereich bis 500kHz untersucht und dabei realistische Umgebungsbedingungen gewählt, wie sie in Photovoltaikanlagen vorherrschen. Es wird experimentell nachgewiesen, dass sich der Lichtbogen als Signal-Spannungsquelle beschreiben lässt. Ein Photovoltaiksystem wird durch die Kleinsignal-Ersatzschaltbilder der einzelnen Komponenten abgebildet und damit ein Modell für Transienten-Simulation erstellt. Damit ist es möglich, einen Störlichtbogen im PV-System simulativ im Frequenzbereich zu bewerten. Es werden verschiedene Konzepte zur Lokalisierung von Störlichtbögen in Photovoltaikanlagen bewertet. Das zielführendste Konzept ist als Prototyp realisiert. Es war in einem Praxistest in einer realen PV-Anlage in der Lage, alle dort gezündeten Lichtbögen korrekt zu lokalisieren.The issue of the present thesis is the investigation, verification and validation of methods for the automatic localization of arcing faults in photovoltaic systems. An area of particular interest is the behavior of the arcing voltage of arcing faults in photovoltaic systems at alterable conditions. The high frequency part of the burning voltage of directional current (DC) arcs were investigated in the frequency range from 1 . . . 500 kHz, and for these investigations the environmental conditions were chosen as they are in real photovoltaik (PV) systems. The current through the arc was varied between 2 . . . 17A, the distance between the electrodes was set from 0,2 . . . 4mm and the electrodes were changed from copper to aluminium and construction steel. As a result, the shapes of the observed power spectral densities differed from the shapes which are described in the literature, in most cases for higher currents. By means of experiments with arcs and a variation of the load impedance, it could be shown that in the high frequency region the arc can be described as a voltage noise source. Based on characterization measurements the equivalent circuits of the parts of a photovoltaic system were parameterized at various working points and therewith a real PV system was modeled as a network. The simulation of series arcs in photovoltaic systems with PSpice showed, in which way the power spectral density of the current behaves for alterable environmental conditions and system configurations. Different concepts for automatic locating an arc fault in a photovoltaik system were evaluated on the basis of simulation results. One of those concepts appeared to be the most reliable and it was realized as a prototype. In a field test, this system was able to locate all arcs, ignited in a real photovoltaik system. Within the scope of the research work, a conference contribution (reviewed) was presented at the „27th International Conference on Electrical Contacts“ (ICEC) 2014 in Dresden (Germany): „HF Characterization of Low Current DC Arcs at Alterable Conditions“ [142] Based on the achieved knowledge, the following inventions are patent pending: 1. DE 102014226999 A1: Verfahren und Vorrichtung zum Erkennen eines Lichtbogens in einer Fotovoltaikanlage [141] 2. DE 102015204376 A1: Verfahren und Vorrichtung zum Erkennen eines Lichtbogens [144] 3. DE 102013219490 A1: Verfahren und Vorrichtung zum Lokalisieren eines Lichtbogens in einem Strompfad einer Fotovoltaikanlage [140] 4. DE 102013219494 A1: Verfahren und Vorrichtung zum Bestimmen einer Modultemperatur eines Photovoltaikmoduls [139] 5. DE 102012217878 A1: Verfahren und Vorrichtung zum Erkennen zumindest einer aktiven Bypassdiode in einem Photovoltaiksystem [90] 6. DE 102014223593 A1: Verfahren und Vorrichtung zum Ermitteln eines Degradationszustandes eines Fotovoltaikmoduls [143]Gegenstand der vorliegenden Arbeit ist die Erforschung, Verifikation und Validierung von Methoden zur automatischen Lokalisierung von Störlichtbögen im Photovoltaiksystem. Von besonderem Interesse ist hierfür das Verhalten der Brennspannung von Störlichtbögen in Photovoltaik- (PV-) Anlagen bei variablen Umgebungsbedingungen. Es wurden systematisch die hochfrequenten Signalanteile der Brennspannung von Gleichstrom-Lichtbögen im Frequenzbereich von 1 . . . 500 kHz untersucht und dabei realistische Umgebungsbedingungen gewählt, wie sie in Photovoltaikanlagen vorherrschen. Der Strom im Lichtbogen wurde von 2 . . . 17A, der Elektrodenabstand von 0,2 . . . 4mm variiert und als Elektrodenmaterialien wurden Kupfer, Aluminium und ein unlegierter Baustahl eingesetzt. Dabei wurde ein von der Literatur abweichender Verlauf des Leistungsdichtespektrums beobachtet, welcher meist für Lichtbögen mit höheren Strömen beschrieben wird. Durch Experimente mit Lichtbögen bei variabler Lastimpedanz konnte gezeigt werden, dass sich der Lichtbogen als hochfrequente Spannungsquelle beschreiben lässt. Basierend auf Charakterisierungsmessungen wurden Ersatzschaltbilder der Bestandteile eines Photovoltaiksystems bei verschiedenen Arbeitspunkten parametrisiert und damit eine reale PV-Anlage als Netzwerk modelliert. Die Simulation von seriellen Störlichtbögen im Photovoltaiksystem mit PSpice zeigte wie sich das Leistungsdichtespektrum des PV-Stroms bei unterschiedlichen Umgebungsbedingungen und Anlagenkonfigurationen verhält. Anhand von Simulationsergebnissen wurden verschiedene Konzepte zur automatischen Lokalisierung von Störlichtbögen in Photovoltaikanlagen bewertet. Das zielführendste Konzept wurde als Prototyp realisiert und einem Praxistest unterzogen. Dieses System war in der Lage, in einer realen Photovoltaikanlage alle dort gezündeten Lichtbögen korrekt zu lokalisieren. Im Rahmen der Forschungsarbeiten entstand ein Konferenzbeitrag (reviewed) zur „27th International Conference on Electrical Contacts“ (ICEC) 2014 in Dresden: „HF Characterization of Low Current DC Arcs at Alterable Conditions“ [142] Aufbauend auf den gewonnenen Erkenntnissen wurden folgende Erfindungen zum Patent angemeldet: 1. DE 102014226999 A1: Verfahren und Vorrichtung zum Erkennen eines Lichtbogens in einer Fotovoltaikanlage [141] 2. DE 102015204376 A1: Verfahren und Vorrichtung zum Erkennen eines Lichtbogens [144] 3. DE 102013219490 A1: Verfahren und Vorrichtung zum Lokalisieren eines Lichtbogens in einem Strompfad einer Fotovoltaikanlage [140] 4. DE 102013219494 A1: Verfahren und Vorrichtung zum Bestimmen einer Modultemperatur eines Photovoltaikmoduls [139] 5. DE 102012217878 A1: Verfahren und Vorrichtung zum Erkennen zumindest einer aktiven Bypassdiode in einem Photovoltaiksystem [90] 6. DE 102014223593 A1: Verfahren und Vorrichtung zum Ermitteln eines Degradationszustandes eines Fotovoltaikmoduls [143

Neoklassischer Marxismus? Wie ideologisch ist die linke Kritik an der Geldpolitik?

A couple of years after the outbreak of the financial crisis, a discussion about money creation from a political economy perspective has finally been initiated again, analyzing the interaction between commercial and central banks. Neo-Marxist approaches, though, are to a large extent unaffected by this discussion – which is based on Joseph Schumpeter’s Theory of Economic Development (1911) – or even completely reject the idea of a money-creation out of nothing. Two Neo-Marxist articles are exemplary of this deficit of monetary theories. On the one hand, the influential book Political Economy of Financial Markets (1999) by Jörg Huffschmid, which has constituted the paradigm of capitalism being driven by financial markets. On the other hand Political Economy of Money (2012) by Stephan Krüger, which assumes that the value of money is still based on the respective production of gold. Consequently, these approaches unintended trigger an adherence to the Neoclassical dichotomy of „real economy“ and „monetary sphere“, albeit with different rationales

Die »angebotspolitische« Wende in der Tarifpolitik: Kritik der aktuellen Lohnpolitik der Gewerkschaften

The »alliance for labour« initiated by the Irade union IG Metall and suggestions of»opening« the sectoral wage contracts dominaled last year's union discussions. Both concepts are based on the adoption of »supply-side policy«-ideas which had been rejected by the trade unions up unlil lhen. Even in view of defeats and economic changes, the Irade union leadership holds on to ils traditional, consensus-oriented strategy