The copy-number tree mixture deconvolution problem and applications to multi-sample bulk sequencing tumor data

Cancer is an evolutionary process driven by somatic mutation. This process can be represented as a phylogenetic tree. Constructing such a phylogenetic tree from genome sequencing data is a challenging task due to the mutational complexity of cancer and the fact that nearly all cancer sequencing is of bulk tissue, measuring a super-position of somatic mutations present in different cells. We study the problem of reconstructing tumor phylogenies from copy number aberrations (CNAs) measured in bulk-sequencing data. We introduce the Copy-Number Tree Mixture Deconvolution (CNTMD) problem, which aims to find the phylogenetic tree with the fewest number of CNAs that explain the copy number data from multiple samples of a tumor. CNTMD generalizes two approaches that have been researched intensively in recent years: deconvolution/factorization algorithms that aim to infer the number and proportions of clones in a mixed tumor sample; and phylogenetic models of copy number evolution that model the dependencies between copy number events that affect the same genomic loci. We design an algorithm for solving the CNTMD problem and apply the algorithm to both simulated and real data. On simulated data, we find that our algorithm outperforms existing approaches that perform either deconvolution or phylogenetic tree construction under the assumption of a single tumor clone per sample. On real data, we analyze multiple samples from a prostate cancer patient, identifying clones within these samples and a phylogenetic tree that relates these clones and their differing proportions across samples. This phylogenetic tree provides a higher-resolution view of copy number evolution of this cancer than published analyses

Negotiating sacred roles:a sociological exploration of priests who are mothers

In 1992, in a historic move, the Church of England voted to allow women's ordination to priesthood and in 1994 the first women priests started to be ordained. Despite much research interest, the experiences of priests who are mothers to dependent children have been minimally investigated. Based on in-depth interviews with seventeen mothers ordained in the Church, this paper will focus on how the sacred-profane boundary is managed. Priests who are mothers have a particular insight into the Church hierarchy as they symbolically straddle the competing discourses of sacred and profane. However, instead of reifying these binaries, the experiences of these women show how such dualisms are challenged and managed in everyday life. Indeed, in terms of experience, ritual, ministry and preaching, priests who are mothers are resisting, recasting and renegotiating sacred terrain in subtle and nuanced ways. Mothers thus not only negotiate the practical and sacramental demands placed on priests, but also illuminate how the sacred domain is regulated and constructed

Computational pan-genomics: Status, promises and challenges

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different Computational methods and paradigms are needed.We will witness the rapid extension of Computational pan-genomics, a new sub-area of research in Computational biology. In this article, we generalize existing definitions and understand a pangenome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a Computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations

Preparation of Vesicles and Nanoparticles of Amphiphilic Cyclodextrins Containing Labile Disulfide Bonds

Amphiphilic cyclodextrin derivatives were prepared in which a disulfide bond connects the hydrophobic substituents to the macrocycle. These compounds were obtained by 1,3-dicyclohexylcarbodiimide-mediated coupling reactions of heptakis(6-amino-6-deoxy)-B-cyclodextrins and disulfide-containing carboxylic acids of increasing hydrophobicity. To improve the water solubility of the cyclodextrins, oligo(ethylene glycol) substituents were grafted to the secondary side of the cyclodextrin molecules. The amphiphilic cyclodextrins form vesicles or nanoparticles in water, which disintegrate in the presence of the disulfide reducing agent dithiothreitol. Hydrophobic guest molecules are released from the nanoparticles upon cleavage of the disulfides

A narrative review of the impact of disbelief in chronic pain

Although the experience of being believed is frequently alluded to in chronic pain literature, few studies have specifically explored this phenomenon and even fewer reviews have been offered. This narrative review sought to explore the wider social context in which individuals with chronic pain may experience disbelief toward their pain. Articles were obtained through a search of eight databases and a hand search of the references of full-text papers. Key results within the articles were noted and integrated to form three main themes: stigma, the experience of isolation, and the experience of emotional distress. The experience of stigma can occur in a number of ways. It may be through actual or perceived encounters with others; it can be through the use of psychologic explanations of pain; it can come through a perceived challenge to one's integrity and subsequently affect an individual's identity; and such stigma may be influenced by negative female stereotypes. The loss of relationships associated with being disbelieved can lead to the experience of isolation. This may be self-initiated, particularly when an individual has been given a contested diagnosis. Finally, disbelief can lead to emotional distress. This can take the form of guilt, depression, and anger. Throughout the article, implications for health care professionals, working with individuals living with chronic pain, are discussed. © 2013 American Society for Pain Management Nursing