Variable neighborhood search for solving the DNA fragment assembly problem

The fragment assembly problem consists in the building of the DNA sequence from several hundreds (or even, thousands) of fragments obtained by biologists in the laboratory. This is an important task in any genome project, since the accuracy of the rest of the phases depends of the result of this stage. In addition, real instances are very large and therefore, the efficiency is also a very important issue in the design of fragment assemblers. In this paper, we propose two Variable Neighborhood Search variants for solving the DNA fragment assembly problem. These algorithms are specifically adapted for the problem being the difference between them the optimization orientation (fitness function). One of them maximizes the Parsons’s fitness function (which only considers the overlapping among the fragments) and the other estimates the variation in the number of contigs during a local search movement, in order to minimize the number of contigs. The results show that doesn’t exist a direct relation between these functions (even in several cases opposite values are generated) although for the tested instances, both variants allow to find similar and very good results but the second option reduces significatively the consumed-time.VIII Workshop de Agentes y Sistemas InteligentesRed de Universidades con Carreras en Informática (RedUNCI

Metaheurísticas aplicadas a la resolución del problema de ensamblado de fragmentos de ADN

En las últimas décadas, importantes avances en la biología molecular y en la tecnología genética subyacente, han provocado un crecimiento inconmensurable en el volumen y variedad de información generada por una vasta comunidad científica. Por ejemplo, el secuenciamiento genético (genome and proteome sequences, en Inglés), la identificación de genes (gene identification), la identificación del perfil de la expresión genética (gene expression profiling) entre otras áreas genéticas, marcaron y marcan la necesidad de involucrar el conocimento de expertos pertenecientes a otras ciencias tales como las matemáticas, las ciencias de la computación, la física y la biología, a los efectos obtener mejores resultados y en menos tiempo. La bioinformática es, entonces, un campo interdisciplinar dedicado a desarrollar técnicas que permitan: analizar secuencias genéticas, identificar y predecir estructuras moleculares, extraer caracter´ısitcas de microarrays de datos, etc.Eje: Agentes y Sistemas InteligentesRed de Universidades con Carreras en Informática (RedUNCI

Metaheurísticas aplicadas a la resolución del problema de ensamblado de fragmentos de ADN

En las últimas décadas, importantes avances en la biología molecular y en la tecnología genética subyacente, han provocado un crecimiento inconmensurable en el volumen y variedad de información generada por una vasta comunidad científica. Por ejemplo, el secuenciamiento genético (genome and proteome sequences, en Inglés), la identificación de genes (gene identification), la identificación del perfil de la expresión genética (gene expression profiling) entre otras áreas genéticas, marcaron y marcan la necesidad de involucrar el conocimento de expertos pertenecientes a otras ciencias tales como las matemáticas, las ciencias de la computación, la física y la biología, a los efectos obtener mejores resultados y en menos tiempo. La bioinformática es, entonces, un campo interdisciplinar dedicado a desarrollar técnicas que permitan: analizar secuencias genéticas, identificar y predecir estructuras moleculares, extraer caracter´ısitcas de microarrays de datos, etc.Eje: Agentes y Sistemas InteligentesRed de Universidades con Carreras en Informática (RedUNCI

Variable neighborhood search for solving the DNA fragment assembly problem

The fragment assembly problem consists in the building of the DNA sequence from several hundreds (or even, thousands) of fragments obtained by biologists in the laboratory. This is an important task in any genome project, since the accuracy of the rest of the phases depends of the result of this stage. In addition, real instances are very large and therefore, the efficiency is also a very important issue in the design of fragment assemblers. In this paper, we propose two Variable Neighborhood Search variants for solving the DNA fragment assembly problem. These algorithms are specifically adapted for the problem being the difference between them the optimization orientation (fitness function). One of them maximizes the Parsons’s fitness function (which only considers the overlapping among the fragments) and the other estimates the variation in the number of contigs during a local search movement, in order to minimize the number of contigs. The results show that doesn’t exist a direct relation between these functions (even in several cases opposite values are generated) although for the tested instances, both variants allow to find similar and very good results but the second option reduces significatively the consumed-time.VIII Workshop de Agentes y Sistemas InteligentesRed de Universidades con Carreras en Informática (RedUNCI

Complex transcription units in Saccharomyces cerevisiae

Overlapping antisense transcription, once thought to be an exceptional event, has become established as a common feature of transcription units. However, despite its prevalence, a bona fide biological consequence or function of overlapping transcription has yet to be ascribed, with the exception of a few locus-specific examples. In this analysis a multi-dimensional systematic approach was employed to interrogate the antisense-producing HMS2 locus. As a result, two additional layers of transcription unit complexity were described: temporal separation of sense and antisense transcription states and transcript-end heterogeneity. Additionally, by observing transcription state-switching in near real time, evidence was provided that links the two phenomena in which changes in the dominant antisense isoform correlate with sense/antisense state switching. Furthermore, in the case of HMS2 regulation, a gene displaying expression periodicity in the metabolic cycle, it was demonstrated that the adoption of sense or antisense states bears consequences at neighbouring loci, showing that modulating antisense transcription can coordinate expression of a cluster of genes. Taken together, this study supports a general model in which sense/antisense state switching at a single locus, modulated by transcriptional regulation of both 5’ and 3’-end promoters, as well as adopting alternative transcript isoforms, can have long-range effects at neighbouring genes, ultimately providing cells with the ability to tailor a wider transcriptional landscape, so that they may adjust their genetic responses to their specific environmental or physiological needs

Genetics and familial risk : establishing the clinician's duty to disclose

The increasing accessibility of personal genetic information creates new challenges for the English Legal System. One of these challenges is the familial nature of genetic information, as screening one individual reveals information about their family unit as a whole. There are potential benefits to disclosing this information, the most important of which is facilitating access to preventative therapies and early treatment. This thesis considers whether clinicians should be subject to a duty to disclose genetic information to those members of a patient’s family who are at the highest risk of sharing genetically transmissible conditions. It is suggested that such a duty could be created through the Tort of Negligence and that such a duty would be consistent with the underlying aims of the tort. This thesis considers the constituent parts of a claim in Negligence – duty, breach and causation – and suggests how these components might be interpreted to, firstly, create a duty to disclose and then, secondly, to give meaningful content to any such a duty. The thesis considers both domestic case law and jurisprudence from America, where a duty to disclose has been created by the courts, and considers whether a similar approach is permissible in English Law. It also examines the current paradigm of confidentiality and data protection and explains why the present legal framework is inadequate and does not provide sufficient legal protection for the relatives of patients harmed as a consequence of nondisclosure. It is the aim of this thesis to advance the debate on the legal implications of the familial aspect of genetic diagnosis and the role of the common law in tackling this challenge. It is also the first work to provide an in depth analysis of a potential duty to disclose genetic risks to the families of patients

Parens Patriae 2.0: Invoking the Superior Courts' Protective Jurisdiction to Help Lonely Older Men Age-in-Place

Loneliness is associated with paradoxically self defeating behaviour, in which social contact is simultaneously desired and rejected. This behaviour can manifest in various ways. Lonely people may, for example, unwittingly decline objectively needed services such as home care. For several reasons, lonely older men may be particularly prone to rejecting offers of support. While refusals are often seen as a win for the right to live at risk, the victory can be hollow when it does not translate into a better quality of life. Often an older man can be persuaded to accept services, but sometimes these efforts fail. In such situations, our traditional understanding of the law leaves concerned third parties with two undesirable options: take no further action or categorise the person as incapable to override his decision making rights. This dilemma is a sad consequence of overcorrecting the medically-dominated approach to elder care with a highly libertarian perspective that lets individuals needlessly suffer. In our pursuit of unfettered individualism, the law has given insufficient weight to internal constraints such as loneliness which affect one’s exercise of free choice, yet keep them below the incapacity threshold. Therefore, in this thesis, I propose an intervention approach to loneliness that is not paralysed by the legal fiction of capacity: invoking a superior court’s protective jurisdiction. Through a therapeutic jurisprudence lens, I draw on the evolution of the parens patriae jurisdiction in Canada and a recent line of English case law to argue that a superior court’s protective jurisdiction may be used to help lonely older men age-in-place. I then propose a framework for invoking the jurisdiction. Specifically, I outline the general circumstances in which a court may be justified in exercising the jurisdiction, and I suggest that dignity ought to serve as the guiding principle. Then using B.C.’s laws as a point of reference, I identify the legislative gap which exists in adult guardianship/protection and mental health laws. Next I propose that the jurisdiction ought to be exercised in the most effective, less intrusive manner. I conclude with a discussion of some practical challenges of using the jurisdiction