Decoding Sequence Classification Models for Acquiring New Biological Insights

Classifying biological sequences is one of the most important tasks in computational biology. In the last decade, support vector machines (SVMs) in combination with sequence kernels have emerged as a de-facto standard. These methods are theoretically well-founded, reliable, and provide high-accuracy solutions at low computational cost. However, obtaining a highly accurate classifier is rarely the end of the story in many practical situations. Instead, one often aims to acquire biological knowledge about the principles underlying a given classification task. SVMs with traditional sequence kernels do not offer a straightforward way of accessing this knowledge.

In this contribution, we propose a new approach to analyzing biological sequences on the basis of support vector machines with sequence kernels. We first extract explicit pattern weights from a given SVM. When classifying a sequence, we then compute a prediction profile by distributing the weight of each pattern to the sequence positions that match the pattern. The final profile not only allows assessing the importance of a position, but also determining for which class it is indicative. Since it is unfeasible to analyze profiles of all sequences in a given data set, we advocate using affinity propagation (AP) clustering to narrow down the analysis to a small set of typical sequences.

The proposed approach is applicable to a wide range of biological sequences and a wide selection of sequence kernels. To illustrate our framework, we present the prediction of oligomerization tendencies of coiled coil proteins as a case study.
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Morfologia e morfometria do forame magno em cães das raças Poodle Toy e Yorkshire terrier

The occipital dysplasia has been characterized by a dorsal enlargement of the foramen magnum which can vary in size and shape. Clinical signs may be present or not in animals with occipital dysplasia. The purpose of this study was to radiographically analyze the morphology and morphometry of the foramen magnum of thirty healthy dogs. This study chose to use fifteen Yorkshire terrier dogs and fifteen Toy Poodle dogs in order to characterize the radiographic aspects of the foramen magnum and contribute to the diagnosis and critical analysis of the occipital dysplasia importance. According to the foramen magnum morphology and tracings, it was possible to classify the radiographic aspects into different shapes varing from oval and quadrangular. Out of 26 (86.7%) animals had a dorsal enlargement and 4 (13.3%) showed normal foramen magnum. Animals without any clinical signs that are radiographically classified as dysplastic dogs may simply represent an anatomic variation of the foramen magnum.A displasia do occipital é o alargamento dorsal do forame magno, o qual pode variar a sua forma e tamanho e os animais com esta alteração morfológica podem ou não apresentar manifestações clínicas. O objetivo desta pesquisa foi avaliar radiograficamente a morfologia e a morfometria do forame magno de 30 cães assintomáticos das raças Poodle toy e Yorkshire terrier, sendo 15 de cada, a fim de se caracterizar os aspectos radiográficos do forame magno e contribuir para o diagnóstico e análise crítica da relevância da displasia do occipital. O forame magno apresentou aspectos que variaram de oval a quadrangular. A presença do alargamento dorsal ocorreu em 26 (86,7%) animais e a ausência em apenas quatro (13,3%). Animais sem manifestações clínicas, que apresentam graus variados de alargamento dorsal e são classificados radiograficamente como displásicos, podem apenas representar variações anatômicas do forame magno

Anxiety and Depression in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations

Real-Time Network Emulation with ns-2

Abstract The network simulator ns-2 implements both wirelessnetworks and emulation- a feature that allows to simulate a network environment among real stations. However,the real-time requirements of a network emulation introduce an inaccurate timing behavior of the simulator scheduler.These timing errors have a negative impact on the performance of network protocols in ns-2. Even more, they lead tofalse simulation results in the IEEE 802.11 protocol implementation. In this paper we present performance improve-ments in ns-2, that increase the accuracy of its virtual clock and the the exactness of the real-time simulation. Then wedescribe a simple time monitoring and correction technique that ensures a timely correct execution of network protocolsand enables wireless network emulation in ns-2. 1

Musik und Begriff. How to do things with Music

(For English, scroll down) Der Text präsentiert drei miteinander verbundene Thesen. (1) Philosophie der Musik modifiziert philosophische Grundbegriffe. (2) Eine gemeinsame Eigenschaft in der Vielfalt der Musikformen liegt im Effekt einer Wahrnehmungsveränderung: oft subtil, unterschwellig und zuweilen als ekstatisch erlebte Selbst- und Welt-Transformation. (3) Strenggenommen nehmen wir nicht Töne wahr, sondern a) unsere Hör-Physiologie wandelt Schwingungsfrequenzen ab circa 18 Hz in Tonhöhen um und damit Zeit-Organisation in ein Raum-Äquivalent. (Musik mit tiefen Tönen an der Grenze zur Wahrnehmung, etwa mittels großer Orgelpfeifen in Kathedralen oder Ton-Anlagen in Nachtclubs, inszeniert genau diesen physiologischen Umschlag, mit potentiellen Transzendenz-Effekten.) b) Wir nehmen einfache Frequenzverhältnisse wie 1:2, 2:3 etc. als (relativ) konsonant wahr, komplexere Verhältnisse als (relativ) dissonant. Die Folge: c) Musikhören verbindet uns mit physikalischem Verhalten von Materie, einschließlich unserer selbst. Hierin gründen rare, musikalisch herausgehobene Eindrücke von Erkenntnis und Enthüllung: das Universum betreffend und unsere Stellung in ihm. The text presents three related claims. (1) Music as a topic of philosophy alters key philosophical concepts; (2) In spite of their vast cultural, historical and contextual differences, all forms of music share the effect of a transformation of perception: ranging from subtle and subliminal to the (rare) experience of ecstatic world- and self-transformations; (3) Strictly speaking, we do not perceive sounds. Rather, a) our hearing-physiology translates frequencies (impulses) of more than 18 Hz into pitch and thus temporal events into quasi-spatial perceptions. Compositions containing very deep sounds (e.g. in cathedrals or in night-clubs) stage exactly this physiological conversion: with potentially ‘transcendence’-like effects. b) We hear simple frequency-ratios such as 1:2, 2:3, 3:4 etc. as (relative) consonances and more complex ones as (relative) dissonances. Thus, c) musical compositions make laws of physical behaviour of matter affectively perceptible. This allows for the occasional impression of musical revelations: regarding the universe, its laws, and our place in it

Kreativität. Eine philosophische Analyse

„Kreativität ist ein sehr junger Begriff und ein sehr altes Phänomen. Sie gilt als unaufklärbares Rätsel, als eine Art „Black Box des Denkens. Dem kollektiven Bewußtsein zufolge ist sie etwas Rares, Flüchtiges, strapaziös zu erzielen und nur wenige Glückliche begünstigend. Das vorliegende Buch präsentiert eine logische Grundidee zur Entstehung von schöpferisch Neuem &#8211 Elemente aus der Informations-, Kommunikations- und Medientheorie verbindend. Diese „Formel wird an philosophischen Stationen von der Antike bis zur Gegenwart erprobt und weiterentwickelt. Kreativität zeigt sich als ein Transformationsphänomen, welches das Denken auf eine andere logische Ebene führt und kategoriale Grenzen kollabieren läßt. Im Ergebnis ist sie nichts per Definition Abwesendes, erreichbar nur über den Umweg von unverfügbarer Gunst, weltabgewandter Passion oder verborgenen Tricks. Kreativität ist vielmehr omnipräsent, schöpferische Energien sind nur mit großem Aufwand zu unterdrücken, und die Frage, wie man sie erreicht, wird zur Frage, wie man ihr eine optimale Basis bereitet, ohne sie wesentlich zu behindern

Ein multidisziplinärer Ansatz

Understanding the relationship between protein sequence and structure is one of the great challenges in biology. Since in the case of the ubiquitous coiled coil motif, structure and occurrence have been described in extensive detail, it might stand to reason that we have a clearly drawn picture of coiled coils. However, the rules for oligomeric formation, and thus the key to biological function, are poorly understood. This work investigates the oligomerization of coiled coils by means of a multidisciplinary approach that combines biochemistry, biophysics, and bioinformatics to shed new light on the formation of two- and three-stranded coiled coils: Based on comprehensive peptide libraries of GCN4 and other coiled coil mutants, the influence of amino acid substitutions on their association is examined. Furthermore, this work uses a machine learning approach to tackle coiled coil oligomerization and identify its underlying rules in the form of weighted amino acid patterns. These rules form the basis of the highly reliable classification tool PrOCoil, which also visualizes the contribution of each individual amino acid to the overall oligomeric tendency of a given coiled coil sequence. Thus, for the first time, a complete network of sequence parameters that influence oligomerization is established, and the underlying rules of coiled-coil formation are presented. This work is rounded off by a methodical contribution. In order for a method to provide a basis for drawing sound conclusions, it must be reviewed carefully. In the case of peptide libraries, little is known about the cross-reactivity between peptides and detection agents. A systematic review and appraisal of the potential of three common read-out systems – 5(6)-TAMRA, FITC, and biotin/streptavidin-POD – to cross- react with individual amino acids in a peptide sequence is therefore presented.Das Verständnis der Beziehung zwischen Sequenz und Struktur von Proteinen ist eine der großen Herausforderungen der heutigen Biologie. Im Falle des weit verbreiteten Coiled- Coil-Motivs sind speziell Struktur und Vorkommen detailliert beschrieben. Es ist also naheliegend, von einer vollständig aufgeklärten Struktur auszugehen. Um so erstaunlicher ist aber, dass die Coiled-Coil-Oligomerisierung – zentrales Kriterium für die biologische Funktion dieser Proteine – nahezu unverstanden ist. In dieser Arbeit wird das Phänomen der Coiled-Coil-Oligomerisierung anhand eines multidisziplinären Ansatzes untersucht. Erst die Kombination aus Biochemie, Biophysik und Bioinformatik erlaubt es, die Formation von zwei- und dreisträngigen Coiled- Coils zu erklären: Zu diesem Zweck wird auf Basis von umfangreichen Peptidbibliotheken von GCN4 und anderen Coiled-Coil-Mutanten der Einfluss von Aminosäure-Substitutionen auf das Assoziationsverhalten untersucht. Weiterhin beschäftigt sich die vorliegende Arbeit mit der Untersuchung des Oligomerisierungsverhaltens von Coiled-Coils. Basierend auf einer neuen Theorie und unter Zuhilfenahme von Support Vector Maschinen werden die der Oligomerisierung zugrundeliegenden Regeln präsentiert. Diese Regeln, in Form von gewichteten Beziehungen zwischen Aminosäuren, bilden die Grundlage eines neuartigen Klassifikations- Tools. "PrOCoil" ist in der Lage, die Stöchiometrie von Coiled-Coils mit außergewöhnlicher Genauigkeit vorherzusagen und den Beitrag einzelner Aminosäuren dazu zu visualisieren. In Form eines Netzwerks von Sequenzparametern wird hier erstmalig ein Modell eingeführt, das in der Lage ist, die Coiled-Coil Oligomerisierung zu erklären. Aus methodischer Sicht feit die Anwendung einer Standard-Methode nicht vor kritischer Reflexion. Unabdingbar für eine zuverlässige Interpretation von Peptidbibliotheken ist das Wissen um potenzielle Kreuzreaktivität von membrangebundenen Peptiden mit den Nachweisreagenzien des Analyten. Daher beinhaltet diese Arbeit als dritten Focus eine Begutachtung und Bewertung von drei in diesem Zusammenhang häufig genutzten Nachweissystemen. 5(6)-TAMRA, FITC und Biotin/ Streptavidin-POD werden auf ihre Kreuzreaktivität mit einzelnen Aminosäuren in Peptidsequenzen hin untersucht