Fault Detection Effectiveness of Metamorphic Relations Developed for Testing Supervised Classifiers

In machine learning, supervised classifiers are used to obtain predictions for unlabeled data by inferring prediction functions using labeled data. Supervised classifiers are widely applied in domains such as computational biology, computational physics and healthcare to make critical decisions. However, it is often hard to test supervised classifiers since the expected answers are unknown. This is commonly known as the \emph{oracle problem} and metamorphic testing (MT) has been used to test such programs. In MT, metamorphic relations (MRs) are developed from intrinsic characteristics of the software under test (SUT). These MRs are used to generate test data and to verify the correctness of the test results without the presence of a test oracle. Effectiveness of MT heavily depends on the MRs used for testing. In this paper we have conducted an extensive empirical study to evaluate the fault detection effectiveness of MRs that have been used in multiple previous studies to test supervised classifiers. Our study uses a total of 709 reachable mutants generated by multiple mutation engines and uses data sets with varying characteristics to test the SUT. Our results reveal that only 14.8\% of these mutants are detected using the MRs and that the fault detection effectiveness of these MRs do not scale with the increased number of mutants when compared to what was reported in previous studies.Comment: 8 pages, AITesting 201

Neural network-based colonoscopic diagnosis using on-line learning and differential evolution

In this paper, on-line training of neural networks is investigated in the context of computer-assisted colonoscopic diagnosis. A memory-based adaptation of the learning rate for the on-line back-propagation (BP) is proposed and used to seed an on-line evolution process that applies a differential evolution (DE) strategy to (re-) adapt the neural network to modified environmental conditions. Our approach looks at on-line training from the perspective of tracking the changing location of an approximate solution of a pattern-based, and thus, dynamically changing, error function. The proposed hybrid strategy is compared with other standard training methods that have traditionally been used for training neural networks off-line. Results in interpreting colonoscopy images and frames of video sequences are promising and suggest that networks trained with this strategy detect malignant regions of interest with accuracy

Functional Characterisation of Alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study has been supported partially by an unrestricted scientific grant from Shire Human Genetic Therapies (Germany

Is the Stack Distance Between Test Case and Method Correlated With Test Effectiveness?

Mutation testing is a means to assess the effectiveness of a test suite and its outcome is considered more meaningful than code coverage metrics. However, despite several optimizations, mutation testing requires a significant computational effort and has not been widely adopted in industry. Therefore, we study in this paper whether test effectiveness can be approximated using a more light-weight approach. We hypothesize that a test case is more likely to detect faults in methods that are close to the test case on the call stack than in methods that the test case accesses indirectly through many other methods. Based on this hypothesis, we propose the minimal stack distance between test case and method as a new test measure, which expresses how close any test case comes to a given method, and study its correlation with test effectiveness. We conducted an empirical study with 21 open-source projects, which comprise in total 1.8 million LOC, and show that a correlation exists between stack distance and test effectiveness. The correlation reaches a strength up to 0.58. We further show that a classifier using the minimal stack distance along with additional easily computable measures can predict the mutation testing result of a method with 92.9% precision and 93.4% recall. Hence, such a classifier can be taken into consideration as a light-weight alternative to mutation testing or as a preceding, less costly step to that.Comment: EASE 201

INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE

Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional omics genomic data to promote the understanding of gene signatures and somatic molecular alterations contributing to cancer progression and clinical outcomes. Following this motivation, my dissertation has been focused on the following three topics in translational genomics. 1) Characterization of transcriptomic plasticity and its association with the tumor microenvironment in glioblastoma (GBM). I have integrated transcriptomic, genomic, protein and clinical data to increase the accuracy of GBM classification, and identify the association between the GBM mesenchymal subtype and reduced tumorpurity, accompanied with increased presence of tumor-associated microglia. Then I have tackled the sole source of microglial as intrinsic tumor bulk but not their corresponding neurosphere cells through both transcriptional and protein level analysis using a panel of sphere-forming glioma cultures and their parent GBM samples.FurthermoreI have demonstrated my hypothesis through longitudinal analysis of paired primary and recurrent GBM samples that the phenotypic alterations of GBM subtypes are not due to intrinsic proneural-to-mesenchymal transition in tumor cells, rather it is intertwined with increased level of microglia upon disease recurrence. Collectively I have elucidated the critical role of tumor microenvironment (Microglia and macrophages from central nervous system) contributing to the intra-tumor heterogeneity and accurate classification of GBM patients based on transcriptomic profiling, which will not only significantly impact on clinical perspective but also pave the way for preclinical cancer research. 2) Identification of prognostic gene signatures that stratify adult diffuse glioma patientsharboring1p/19q co-deletions. I have compared multiple statistical methods and derived a gene signature significantly associated with survival by applying a machine learning algorithm. Then I have identified inflammatory response and acetylation activity that associated with malignant progression of 1p/19q co-deleted glioma. In addition, I showed this signature translates to other types of adult diffuse glioma, suggesting its universality in the pathobiology of other subset gliomas. My efforts on integrative data analysis of this highly curated data set usingoptimizedstatistical models will reflect the pending update to WHO classification system oftumorsin the central nervous system (CNS). 3) Comprehensive characterization of somatic fusion transcripts in Pan-Cancers. I have identified a panel of novel fusion transcripts across all of TCGA cancer types through transcriptomic profiling. Then I have predicted fusion proteins with kinase activity and hub function of pathway network based on the annotation of genetically mobile domains and functional domain architectures. I have evaluated a panel of in -frame gene fusions as potential driver mutations based on network fusion centrality hypothesis. I have also characterised the emerging complexity of genetic architecture in fusion transcripts through integrating genomic structure and somatic variants and delineating the distinct genomic patterns of fusion events across different cancer types. Overall my exploration of the pathogenetic impact and clinical relevance of candidate gene fusions have provided fundamental insights into the management of a subset of cancer patients by predicting the oncogenic signalling and specific drug targets encoded by these fusion genes. Taken together, the translational genomic research I have conducted during my Ph.D. study will shed new light on precision medicine and contribute to the cancer research community. The novel classification concept, gene signature and fusion transcripts I have identified will address several hotly debated issues in translational genomics, such as complex interactions between tumor bulks and their adjacent microenvironments, prognostic markers for clinical diagnostics and personalized therapy, distinct patterns of genomic structure alterations and oncogenic events in different cancer types, therefore facilitating our understanding of genomic alterations and moving us towards the development of precision medicine

Zn(II)-curc targets p53 in thyroid cancer cells

P53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers