1,721,129 research outputs found
Effects of Natural and Synthetic Retinoids on the Differentiation and Growth of Squamous Cancers
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Abstract 3587: Intratumoral divergence of copy number alterations in NSCLC
No full textAbstract
Intratumoral heterogeneity has been increasingly established as a critical phenotype of cancer genomes. Its characterization at the DNA level is based on the identification of somatic mutations consisting of single nucleotide variants (SNVs) and copy number alterations (CNAs), which include deletions, amplifications, and copy neutral loss of heterozygosity. Currently, most methods for the detection of intratumoral heterogeneity use an implicit “infinite sites” model for both SNVs and CNAs. While this may often be appropriate for SNVs, we demonstrate its violation for CNAs in unstable cancer genomes. Here, we propose a novel method to identify CNAs that were created by independent mutational events but alter the same genomic region. Our method identifies regions where the germline heterozygous signals (allelic intensities for DNA arrays or frequencies for next-generation sequencing) shift toward different parental haplotypes between different samples from the same tumor, thus indicative of divergent tumor clones. In this context we define a divergent CNA as one found on multiple samples from the same tumor but with different chromosomal changes giving rise to the CNAs. We applied our method to data from core needle biopsies extracted from the tumors of 31 non-small cell lung cancer (NSCLC) patients and processed using Illumina SNP arrays. We overlapped CNA calls from the same tumor, and then tested whether overlapping segments showed divergent CNAs. We observe instances of divergent CNAs in 23 of the 31 patient tumors comprising 260 in total (median = 5 divergent CNAs per tumor). Strikingly, one tumor had 34. We then assessed whether the level of recurrent mutation correlated with clinical or genomic features. While there was no association with smoking or histology, we did observe a positive association between the rate of divergence and somatic mutations (including loss) in putative genome “gatekeeper” genes, p53 and CDKN2A (P = 0.001). We detected divergent CNAs that spanned shared genomic regions in three or more NSCLC tumors. These included large (> 1Mb) events in chromosome 6 (q13-14, q21-22, q25) and chromosome 21 (q22), as well as smaller events, which included the integrin collagen receptor locus ITGA1-PELO-ITGA2, 8p23.1, 8q24.3, 18q11.2 (ZNF521 gene), and 21q21.3, which has bindings sites for GATA2, GATA3, and STAT3. Our observed divergent genomic alterations represent half of the total number expected since imbalances of the same haplotype will not be observable in such data. In summary, our approach allows for the detection of genomic regions that are divergently altered. This information may support methods to identify CNAs under positive or negative selection in the tumor microenvironment as well as regions of increased genomic instability. This provides an added dimension to intratumoral heterogeneity analysis for a more comprehensive characterization of cancer genomes.
Citation Format: Yasminka A. Jakubek, Smruthy Sivakumar, Louise C. Strong, Humam Kadara, Paul Scheet. Intratumoral divergence of copy number alterations in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3587. doi:10.1158/1538-7445.AM2017-3587</jats:p
Abstract 2594: Optimizing the replication of cancer genomics workflows: case studies
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Reproducing results is a major issue in cancer biology, whose “work bench” is dynamic and complex, with frequently updated algorithms and software. The better to manage our work in this environment we have developed SyQADA, a System for Quality-Assured Data Analysis – a workflow automation system designed to simplify common sequential analysis processes on the same or different data. SyQADA manages many of the details of procedural bookkeeping involved in bioinformatics workflows: What samples are we using? Where are the raw data? Were all the samples processed? Did every job complete satisfactorily? Is there as much output as expected? Where are the input files for the next step? How long does a typical job take to run? Which program versions did we use? Can we easily compare these results with the output of a different version of a program, or with different input data?
Using SyQADA, we have found ourselves better able to reproduce results while at the same time reducing the human effort required to manage our upstream data analyses. Here, we briefly describe how our lung cancer studies have benefitted from the use of SyQADA.
To understand the effect of different variant callers for Ion Torrent deep sequencing data in a lung cancer genomics study, we created a work protocol that allowed us to compare the different sets of variants called on 34 distinct somatic DNA samples from 4 patients. This complex processing framework involved running multiple variant callers, annotating variants, filtering germline variants using quality control metrics, and collating results across samples and callers. With SyQADA, we were able to re-run individual processes changing parameters with trivial changes to our configuration, yielding improved output. We then applied that unmodified protocol to the 500 samples from 48 individuals in our study, and rapidly produced data from which we could perform biological analysis. We then applied the protocol to a study of pre-malignant lesions in 25 lung cancer patients. In both studies, our workflow allowed us to generate comparable results in a matter of hours rather than days.
SyQADA has been used by individuals with backgrounds ranging from expert programmer to Unix novice, to perform and repeat dozens of diverse analytical workflows. Projects to which SyQADA has been applied include allelic imbalance studies of TCGA samples for cancers of the breast, pancreas, lung, and colon, processing roughly 6000 samples through a dozen steps.
A zipfile containing the SyQADA executable source code, documentation, tutorial examples, and workflows used in our lab will be available.
Citation Format: Jerry Fowler, F. Anthony San Lucas, Smruthy Sivakumar, Aditya Deshpande, Humam Kadara, Paul A. Scheet. Optimizing the replication of cancer genomics workflows: case studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2594. doi:10.1158/1538-7445.AM2017-2594</jats:p
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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