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Search Results: 1 - 10 of 18437 matches for " Patrick Tan "
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Germline polymorphisms as modulators of cancer phenotypes
Patrick Tan
BMC Medicine , 2008, DOI: 10.1186/1741-7015-6-27
Abstract: A major advancement of genetic research in recent years has been the explosion of genome-wide association studies (GWAS) in the literature from different investigators and laboratories [1]. The completion of the reference human genome sequence, and its subsequent comparison across different human sub-populations, has identified millions of genetic polymorphisms that differ between different individuals, families, and ethnic groups [2]. With the availability of increasingly affordable chip technologies for interrogating these polymorphisms en masse in individual genomes, it is now possible to consider identifying, on a comprehensive genome-wide scale, all genes and genetic variants associated with human disease. In the area of cancer, GWAS studies have been performed for multiple different tumor types including breast, lung, and stomach cancers [3-5]. These studies have both reconfirmed previously known disease genes (eg FGFR2 in breast cancer) [3], and also identified novel genetic loci, such as TNRC9, MAP3K1, and LSP1 for breast cancer [3] and the nicotinic acetylcholine receptor subunits in lung cancer [4]. To date, the majority of reported GWAS studies have employed a case-control design, where affected individuals with a disease are compared against a matched population of non-affected normal controls. The genetic variants identified using such case-control designs thus represent 'disease susceptibility' loci that can either increase or decrease an individual's risk to developing disease. A report published this month in BMC Medicine by Van Ness et al. [6] seeks to extend this theme, by asking whether germline polymorphisms can influence not simply the onset of disease, but the actual course of disease prognosis in cancer.The focus of Van Ness et al. on the cancer patient germline is particularly notable when one considers how the concept of cancer as an acquired somatic disease has dominated the field. In this model, tumor cells are believed to arise as a conse
A model for the onset of oscillations near the stopping angle in an inclined granular flow
Danielle Tan,Patrick Richard,James T. Jenkins
Physics , 2013, DOI: 10.1140/epje/i2012-12122-x
Abstract: We propose an explanation for the onset of oscillations seen in numerical simulations of dense, inclined flows of inelastic, frictional spheres. It is based on a phase transition between disordered and ordered collisional states that may be interrupted by the formation of force chains. Low frequency oscillations between ordered and disordered states take place over weakly bumpy bases; higher-frequency oscillations over strongly bumpy bases involve the formation of particle chains that extend to the base and interrupt the phase change. The predicted frequency and amplitude of the oscillations induced by the unstable part of the equation of state are similar to those seen in the simulations and they depend upon the contact stiffness in the same way. Such oscillations could be the source of sound produced by flowing sand.
Integrative Functional Genomics in Cancer Research and Its Clinical Implications
Kumaresan Ganesan,Saikat Banerjee,Paramasamy Gunasekaran,Patrick Tan
Journal of Cancer Molecules , 2010,
Abstract: Many cancer predisposition and causative genes have been identified in the past few decades and have been extensively evaluated in primary tumors. The complex and highly heterogeneous nature of tumors requires more clinically useful candidate genes as prognostic, diagnostic, and therapeutic biomarkers for different subtypes of tumors and for predicting therapeutic response. Although genomics platforms have revealed the complex nature of tumors, integrative functional genomics approaches have the potential to provide a holistic understanding of the molecular genomic processes of carcinogenesis. While integration of the data gathered from genome and transcriptome is the simplest approach in integrative genomics, these approaches are also extended to analyze different levels of information, different cancer model systems, and multiple studies. Recent studies have revealed that integrative genomics has the potential to revolutionize the diagnosis and management of cancer by offering an unprecedented comprehensive understanding of cancer through unbiased experimental approaches.
Helping Students Test Programs That Have Graphical User Interfaces
Matthew Thornton,Stephen H. Edwards,Roy Patrick Tan
Journal of Systemics, Cybernetics and Informatics , 2008,
Abstract: Within computer science education, many educators are incorporating software testing activities into regular programming assignments. Tools like JUnit and its relatives make software testing tasks much easier, bringing them into the realm of even introductory students. At the same time, many introductory programming courses are now including graphical interfaces as part of student assignments to improve student interest and engagement. Unfortunately, writing software tests for programs that have significant graphical user interfaces is beyond the skills of typical students (and many educators). This paper presents initial work at combining educationally oriented and open-source tools to create an infrastructure for writing tests for Java programs that have graphical user interfaces. Critically, these tools are intended to be appropriate for introductory (CS1/CS2) student use, and to dovetail with current teaching approaches that incorporate software testing in programming assignments. We also include in our findings our proposed approach to evaluating our techniques.
Chaos and Robustness in a Single Family of Genetic Oscillatory Networks
Daniel Fu, Patrick Tan, Alexey Kuznetsov, Yaroslav I. Molkov
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090666
Abstract: Genetic oscillatory networks can be mathematically modeled with delay differential equations (DDEs). Interpreting genetic networks with DDEs gives a more intuitive understanding from a biological standpoint. However, it presents a problem mathematically, for DDEs are by construction infinitely-dimensional and thus cannot be analyzed using methods common for systems of ordinary differential equations (ODEs). In our study, we address this problem by developing a method for reducing infinitely-dimensional DDEs to two- and three-dimensional systems of ODEs. We find that the three-dimensional reductions provide qualitative improvements over the two-dimensional reductions. We find that the reducibility of a DDE corresponds to its robustness. For non-robust DDEs that exhibit high-dimensional dynamics, we calculate analytic dimension lines to predict the dependence of the DDEs’ correlation dimension on parameters. From these lines, we deduce that the correlation dimension of non-robust DDEs grows linearly with the delay. On the other hand, for robust DDEs, we find that the period of oscillation grows linearly with delay. We find that DDEs with exclusively negative feedback are robust, whereas DDEs with feedback that changes its sign are not robust. We find that non-saturable degradation damps oscillations and narrows the range of parameter values for which oscillations exist. Finally, we deduce that natural genetic oscillators with highly-regular periods likely have solely negative feedback.
Internet Use and Its Impact on Engagement in Leisure Activities in China
Ronggang Zhou, Patrick S. W. Fong, Peking Tan
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089598
Abstract: Introduction Internet use has become an increasingly common leisure time activity among Chinese citizens. The association between Internet use and engagement in leisure activities is especially unclear among China population. This study aims to investigate Internet usage and to determine whether active Internet use is a marker for low or high levels of leisure time activities. Methods/Principal Findings With the use of a face-to-face structured questionnaire interview, a total of 2,400 respondents who met all screening requirements were surveyed to answer the questions in eight major cities in China. 66.2% (n = 1,589) of all respondents were identified as Internet users. Of these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as “informative or instrumental users,” “entertainment users,” “communication users,” and “advanced users,” respectively. Regarding time spent on Internet use in leisure time, more than 96% reported going online in non-work situations, and 26.2% (n = 416) were classified as “heavy Internet users.” A logistic regression analysis revealed that there were significant differences in some leisure activities between non-Internet users and Internet users, with an observed one-unit increase in the leisure time dependence category increasing the probability of engaging in mental or social activities. In contrast, Internet users were less engaged in physical exercise-related activities. In addition, advanced Internet users were generally more active in leisure time activities than non-Internet users and other types of users. Conclusion/Significance Internet use is one of very common leisure activities in Chinese citizens, and age, gender, income, and education are the key factors affecting Internet access. According to different types of leisure activities, Internet usage has different impacts on leisure activity engagement. High Internet dependence has no significant negative influence on engagement in mental or social leisure activities, but this group respondent tended to be less engaged in physical activities.
Large-Scale Analysis of Gene Expression and Connectivity in the Rodent Brain: Insights through Data Integration
Leon French,Powell Patrick Cheng Tan,Paul Pavlidis
Frontiers in Neuroinformatics , 2011, DOI: 10.3389/fninf.2011.00012
Abstract: Recent research in C. elegans and the rodent has identified correlations between gene expression and connectivity. Here we extend this type of approach to examine complex patterns of gene expression in the rodent brain in the context of regional brain connectivity and differences in cellular populations. Using multiple large-scale data sets obtained from public sources, we identified two novel patterns of mouse brain gene expression showing a strong degree of anti-correlation, and relate this to multiple data modalities including macroscale connectivity. We found that these signatures are associated with differences in expression of neuronal and oligodendrocyte markers, suggesting they reflect regional differences in cellular populations. We also find that the expression level of these genes is correlated with connectivity degree, with regions expressing the neuron-enriched pattern having more incoming and outgoing connections with other regions. Our results exemplify what is possible when increasingly detailed large-scale cell- and gene-level data sets are integrated with connectivity data.
PORCN Moonlights in a Wnt-Independent Pathway That Regulates Cancer Cell Proliferation
Tracy M. Covey, Simran Kaur, Tina Tan Ong, Kyle D. Proffitt, Yonghui Wu, Patrick Tan, David M. Virshup
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034532
Abstract: Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was required for the proliferation of transformed cells. Knockdown of PORCN by multiple independent siRNAs results in a cell growth defect in a subset of epithelial cancer cell lines. The growth defect is transformation-dependent in human mammary epithelial (HMEC) cells. Additionally, inducible PORCN knockdown by two independent shRNAs markedly reduces the growth of established MDA-MB-231 cancers in orthotopic xenografts in immunodeficient mice. Unexpectedly, the proliferation defect resulting from loss of PORCN occurs in a Wnt-independent manner, as it is rescued by re-expression of catalytically inactive PORCN, and is not seen after RNAi-mediated knockdown of the Wnt carrier protein WLS, nor after treatment with the PORCN inhibitor IWP. Consistent with a role in a Wnt-independent pathway, knockdown of PORCN regulates a distinct set of genes that are not altered by other inhibitors of Wnt signaling. PORCN protein thus appears to moonlight in a novel signaling pathway that is rate-limiting for cancer cell growth and tumorigenesis independent of its enzymatic function in Wnt biosynthesis and secretion.
Assessing Matched Normal and Tumor Pairs in Next-Generation Sequencing Studies
Liang Goh,Geng Bo Chen,Ioana Cutcutache,Benjamin Low,Bin Tean Teh,Steve Rozen,Patrick Tan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017810
Abstract: Next generation sequencing technology has revolutionized the study of cancers. Through matched normal-tumor pairs, it is now possible to identify genome-wide germline and somatic mutations. The generation and analysis of the data requires rigorous quality checks and filtering, and the current analytical pipeline is constantly undergoing improvements. We noted however that in analyzing matched pairs, there is an implicit assumption that the sequenced data are matched, without any quality check such as those implemented in association studies. There are serious implications in this assumption as identification of germline and rare somatic variants depend on the normal sample being the matched pair. Using a genetics concept on measuring relatedness between individuals, we demonstrate that the matchedness of tumor pairs can be quantified and should be included as part of a quality protocol in analysis of sequenced data. Despite the mutation changes in cancer samples, matched tumor-normal pairs are still relatively similar in sequence compared to non-matched pairs. We demonstrate that the approach can be used to assess the mutation landscape between individuals.
Finding exclusively deleted or amplified genomic areas in lung adenocarcinomas using a novel chromosomal pattern analysis
Philippe Bro?t, Patrick Tan, Marco Alifano, Sophie Camilleri-Bro?t, Sylvia Richardson
BMC Medical Genomics , 2009, DOI: 10.1186/1755-8794-2-43
Abstract: We propose to identify patterns of recurrent CNAs across tumor samples from high-resolution comparative genomic hybridization microarrays. Clustering is achieved by modeling the copy number state (loss, no-change, gain) as a multinomial distribution with probabilities parameterized through a latent class model leading to nine patterns of recurrent CNAs. This model gives us a powerful tool to identify clones with contrasting propensity of being deleted or amplified across tumor samples. We applied this model to a homogeneous series of 65 lung adenocarcinomas.Our latent class model analysis identified interesting patterns of chromosomal aberrations. Our results showed that about thirty percent of the genomic clones were classified either as "exclusively" deleted or amplified recurrent CNAs and could be considered as non random chromosomal events. Most of the known oncogenes or tumor suppressor genes associated with lung adenocarcinoma were located within these areas. We also describe genomic areas of potential interest and show that an increase of the frequency of amplification in these particular areas is significantly associated with poorer survival.Analyzing jointly deletions and amplifications through our latent class model analysis allows highlighting specific genomic areas with exclusively amplified or deleted recurrent CNAs which are good candidate for harboring oncogenes or tumor suppressor genes.Chromosomal instability plays an important role in carcinogenesis with numerical and structural genomic alteration leading to selective growth advantages [1]. In recent years, high-resolution array comparative genomic hybridization (aCGH) has replaced conventional metaphase CGH as the standard protocol for identifying segmental copy number alteration across the whole genome. The classical strategy of aCGH technique is to co-hybridize genomic DNA from a cancer sample (labelled with one fluorochrome) with genomic DNA from a normal reference sample (labelled with a diffe
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