Cancer is in general not a result of an abnormality of a single gene but a consequence of changes in many genes, it is therefore of great importance to understand the roles of different oncogenic and tumor suppressor pathways in tumorigenesis. In recent years, there have been many computational models developed to study the genetic alterations of different pathways in the evolutionary process of cancer. However, most of the methods are knowledge-based enrichment analyses and inflexible to analyze user-defined pathways or gene sets. In this paper, we develop a nonparametric and data-driven approach to testing for the dynamic changes of pathways over the cancer progression. Our method is based on an expansion and refinement of the pathway being studied, followed by a graph-based multivariate test, which is very easy to implement in practice. The new test is applied to the rich Cancer Genome Atlas data to study the (epi)genetic alterations of 186 KEGG pathways in the development of serous ovarian cancer. To make use of the comprehensive data, we incorporate three data types in the analysis representing gene expression level, copy number and DNA methylation level. Our analysis suggests a list of nine pathways that are closely associated with serous ovarian cancer progression, including cell cycle, ERBB, JAK-STAT signaling and p53 signaling pathways. By pairwise tests, we found that most of the identified pathways contribute only to a particular transition step. For instance, the cell cycle and ERBB pathways play key roles in the early-stage transition, while the ECM receptor and apoptosis pathways contribute to the progression from stage III to stage IV. The proposed computational pipeline is powerful in detecting important pathways and gene sets that drive cancers at certain stage(s). It offers new insights into the understanding of molecular mechanism of cancer initiation and progression. © 2020 Elsevier Ltd
Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated d
The development of better tools for diagnosis and more accurate prognosis of cancer includes the search for biomarkers; molecules whose presence, absence or change in quantity or structure is associated with a particular tumour or prognosis/therapeutic outcome. While biomarkers need not be functionally relevant, if cell survival, then they could also provide new targets for therapeutic drugs. In recent years attention has been applied to a group of proteins known as cancer testis antigens (CT antigens) [1]. These proteins are products of genes whose expression was normally confined to the testis, yet they are expressed in tumour cells. CT genes are bound to serve a wide array of roles in the testes, which have many highly differentiated cel
... Show MoreBackground: The association between facial types and dental arches forms has considerable implications in orthodontic diagnosis and treatment planning. The aim was to establish the maxillary and mandibular dental arches width and length in skeletal and dental class II division 1 and class III malocclusion groups, find out the most frequent dental arch form and facial type and the association between them and to check the gender differences. Materials and Methods: Frontal and lateral facial photographs and maxillary and mandibular occlussal photographs for 90 iraqi subjects with age 18-25 years old (45 males and 45 females) divided equally into three groups, the 1st group with class II division 1malocclusion (overjet more than 3mm but less t
... Show MoreThis study focused on a fundamental issue which was represented by ability of Iraqi central bank in facing the difficulty of determining the optimal ratio of liquidity in the Iraqi banks in terms of the balancing between its obligations to the depositors and borrowers, and liquidate their funds on one hand and the risks on the other hand.the search aimed for achieving the goals which represented by identifying the possibility of Iraqi banks to apply the regulations rules and instructions issued by central bank of Iraq in determining ratio of liquidity and its appropriate with Iraqi banks action to implement a reasonable profit to&
... Show MoreAssessing performance efficiency is critical to the management need for oversight, planning, and continuous periodic evaluation of the multiple activities of Northern Cement State Company in order to determine the level of achievement of the objectives set, and to correct the deviations and delays that the evaluation shows and limitation of liability. What cannot be measured cannot be managed. The aim of this research is to highlight the impact of using BSC, financial and non-financial, to give comprehensive and clear picture of the company's performance and to measure the quality of its performance by using six-sigma and the level of deviations in achieving the planned goals. Therefore, four-key hypotheses were formulated for th
... Show MoreThis research aims at shedding light on the concept of insurance awareness and clarifying its role on marketing insurance services of a sample of (100) employees in the National Company for Insurance. Questionnaire is used as a main instrument for collecting data and information from the sample. Their answers were analyzed by using arithmetic means, standard deviation, centesimal weight, and the correlation coefficient ( , F, t) tests .The research reached several conclusions of which:1.The sample member's response to insurance awareness and marketing insurance services factors was in the medium level.2.There was a positive relationship of a moral sign between insurance awareness and marketing insurance services, that correlation coeffic
... Show MoreThe research aimed at measuring the compatibility of Big date with the organizational Ambidexterity dimensions of the Asia cell Mobile telecommunications company in Iraq in order to determine the possibility of adoption of Big data Triple as a approach to achieve organizational Ambidexterity.
The study adopted the descriptive analytical approach to collect and analyze the data collected by the questionnaire tool developed on the Likert scale After a comprehensive review of the literature related to the two basic study dimensions, the data has been subjected to many statistical treatments in accordance with res
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