Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

The MaSuRCA genome assembler

Abstract: Motivation. Second-generation sequencing technologies produce high coverage of the genome by short reads at a very low cost, which has prompted development of new assembly methods. In particular, multiple algorithms based on de Bruijn graphs have been shown to be effective for the assembly problem. In this paper we describe a new hybrid approach that has the computational efficiency of de Bruijn graph methods and the flexibility of overlap-based assembly strategies, and which allows variable read lengths while tolerating a significant level of sequencing error. Our method transforms very large numbers of paired-end reads into a much smaller number of longer “super-reads.” The use of super-reads allows us to assemble combinations of Illumina reads of differing lengths together with longer reads from 454 and Sanger sequencing technologies, making it one of the few assemblers capable of handling such mixtures. We call our system the Maryland Super-Read Celera Assembler (abbreviated MaSuRCA and pronounced “mazurka”). Results. We evaluate the performance of MaSuRCA against two of the most widely used assemblers for Illumina data, Allpaths-LG and SOAPdenovo2, on two data sets from organisms for which highquality assemblies are available: the bacterium Rhodobacter sphaeroides and chromosome 16 of the mouse genome. We show that MaSuRCA performs on par or better than Allpaths-LG and significantly better than SOAPdenovo on these data, when evaluated against the finished sequence. We then show that MaSuRCA can significantly improve its assemblies when the original data are augmented with long reads. Availability. MaSuRCA is available as open-source code at ftp://ftp.genome.umd.edu/pub/MaSuRCA/. Previous (pre-publication) releases have been publicly available for over a year. Contact. Aleksey Zimin, alekseyz@ipst.umd.edu

Pain catastrophizing: a critical review

Abstract: Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with a number of important pain-related outcomes. In the present review, we first focus our efforts on the conceptualization of pain catastrophizing, highlighting its conceptual history and potential problem areas. We then focus our discussion on a number of theoretical mechanisms of action: appraisal theory, attention bias/information processing, communal coping, CNS pain processing mechanisms, psychophysiological pathways and neural pathways. We then offer evidence to suggest that pain catastrophizing represents an important process factor in pain treatment. We conclude by offering what we believe represents an integrated heuristic model for use by researchers over the next 5 years; a model we believe will advance the field most expediently.

Ligand-Independent Androgen Receptor Variants Derived from Splicing of Cryptic Exons Signify Hormone-Refractory Prostate Cancer

Abstract: Suppression of androgen production and function provides palliation but not cure in men with prostate cancer (PCa). Therapeutic failure and progression to hormone-refractory PCa (HRPC) are often accompanied by molecular alterations involving the androgen receptor (AR). In this study, we report novel forms of AR alteration that are prevalent in HRPC. Through in silico sequence analysis and subsequent experimental validation studies, we uncovered seven AR variant transcripts lacking the reading frames for the ligand-binding domain due to splicing of "intronic" cryptic exons to the upstream exons encoding the AR DNA-binding domain. We focused on the two most abundantly expressed variants, AR-V1 and AR-V7, for more detailed analysis. AR-V1 and AR-V7 mRNA showed an average 20-fold higher expression in HRPC (n = 25) when compared with hormone-naive PCa (n = 82; P < 0.0001). Among the hormone-naive PCa, higher expression of AR-V7 predicted biochemical recurrence following surgical treatment (P = 0.012). Polyclonal antibodies specific to AR-V7 detected the AR-V7 protein frequently in HRPC specimens but rarely in hormone-naive PCa specimens. AR-V7 was localized in the nuclei of cultured PCa cells under androgen-depleted conditions, and constitutively active in driving the expression of canonical androgen-responsive genes, as revealed by both AR reporter assays and expression microarray analysis. These results suggest a novel mechanism for the development of HRPC that warrants further investigation. In addition, as expression markers for lethal PCa, these novel AR variants may be explored as potential biomarkers and therapeutic targets for advanced PCa.