Structured Review of the Evidence for Effects of Code Duplication on Software Quality

This report presents the detailed steps and results of a structured review of code clone literature. The aim of the review is to investigate the evidence for the claim that code duplication has a negative effect on code changeability. This report contains only the details of the review for which there is not enough place to include them in the companion paper published at a conference (Hordijk, Ponisio et al. 2009 - Harmfulness of Code Duplication - A Structured Review of the Evidence)

TCR Convergence in Individuals Treated With Immune Checkpoint Inhibition for Cancer.

Tumor antigen-driven selection may expand T cells having T cell receptors (TCRs) of shared antigen specificity but different amino acid or nucleotide sequence in a process known as TCR convergence. Substitution sequencing errors introduced by TCRβ (TCRB) repertoire sequencing may create artifacts resembling TCR convergence. Given the anticipated differences in substitution error rates across different next-generation sequencing platforms, the choice of platform could be consequential. To test this, we performed TCRB sequencing on the same peripheral blood mononuclear cells (PBMC) from individuals with cancer receiving anti-CTLA-4 or anti-PD-1 using an Illumina-based approach (Sequenta) and an Ion Torrent-based approach (Oncomine TCRB-LR). While both approaches found similar TCR diversity, clonality, and clonal overlap, we found that Illumina-based sequencing resulted in higher TCR convergence than with the Ion Torrent approach. To build upon this initial observation we conducted a systematic comparison of Illumina-based TCRB sequencing assays, including those employing molecular barcodes, with the Oncomine assay, revealing differences in the frequency of convergent events, purportedly artifactual rearrangements, and sensitivity of detection. Finally, we applied the Ion Torrent-based approach to evaluate clonality and convergence in a cohort of individuals receiving anti-CTLA-4 blockade for cancer. We found that clonality and convergence independently predicted response and could be combined to improve the accuracy of a logistic regression classifier. These results demonstrate the importance of the sequencing platform in assessing TCRB convergence

Determining cellular CTCF and cohesin abundances to constrain 3D genome models.

Achieving a quantitative and predictive understanding of 3D genome architecture remains a major challenge, as it requires quantitative measurements of the key proteins involved. Here, we report the quantification of CTCF and cohesin, two causal regulators of topologically associating domains (TADs) in mammalian cells. Extending our previous imaging studies (Hansen et al., 2017), we estimate bounds on the density of putatively DNA loop-extruding cohesin complexes and CTCF binding site occupancy. Furthermore, co-immunoprecipitation studies of an endogenously tagged subunit (Rad21) suggest the presence of cohesin dimers and/or oligomers. Finally, based on our cell lines with accurately measured protein abundances, we report a method to conveniently determine the number of molecules of any Halo-tagged protein in the cell. We anticipate that our results and the established tool for measuring cellular protein abundances will advance a more quantitative understanding of 3D genome organization, and facilitate protein quantification, key to comprehend diverse biological processes

Towards Collaborative Scientific Workflow Management System

The big data explosion phenomenon has impacted several domains, starting from research areas to divergent of business models in recent years. As this intensive amount of data opens up the possibilities of several interesting knowledge discoveries, over the past few years divergent of research domains have undergone the shift of trend towards analyzing those massive amount data. Scientific Workflow Management System (SWfMS) has gained much popularity in recent years in accelerating those data-intensive analyses, visualization, and discoveries of important information. Data-intensive tasks are often significantly time-consuming and complex in nature and hence SWfMSs are designed to efficiently support the specification, modification, execution, failure handling, and monitoring of the tasks in a scientific workflow. As far as the complexity, dimension, and volume of data are concerned, their effective analysis or management often become challenging for an individual and requires collaboration of multiple scientists instead. Hence, the notion of 'Collaborative SWfMS' was coined - which gained significant interest among researchers in recent years as none of the existing SWfMSs directly support real-time collaboration among scientists. In terms of collaborative SWfMSs, consistency management in the face of conflicting concurrent operations of the collaborators is a major challenge for its highly interconnected document structure among the computational modules - where any minor change in a part of the workflow can highly impact the other part of the collaborative workflow for the datalink relation among them. In addition to the consistency management, studies show several other challenges that need to be addressed towards a successful design of collaborative SWfMSs, such as sub-workflow composition and execution by different sub-groups, relationship between scientific workflows and collaboration models, sub-workflow monitoring, seamless integration and access control of the workflow components among collaborators and so on. In this thesis, we propose a locking scheme to facilitate consistency management in collaborative SWfMSs. The proposed method works by locking workflow components at a granular attribute level in addition to supporting locks on a targeted part of the collaborative workflow. We conducted several experiments to analyze the performance of the proposed method in comparison to related existing methods. Our studies show that the proposed method can reduce the average waiting time of a collaborator by up to 36% while increasing the average workflow update rate by up to 15% in comparison to existing descendent modular level locking techniques for collaborative SWfMSs. We also propose a role-based access control technique for the management of collaborative SWfMSs. We leverage the Collaborative Interactive Application Methodology (CIAM) for the investigation of role-based access control in the context of collaborative SWfMSs. We present our proposed method with a use-case of Plant Phenotyping and Genotyping research domain. Recent study shows that the collaborative SWfMSs often different sets of opportunities and challenges. From our investigations on existing research works towards collaborative SWfMSs and findings of our prior two studies, we propose an architecture of collaborative SWfMSs. We propose - SciWorCS - a Collaborative Scientific Workflow Management System as a proof of concept of the proposed architecture; which is the first of its kind to the best of our knowledge. We present several real-world use-cases of scientific workflows using SciWorCS. Finally, we conduct several user studies using SciWorCS comprising different real-world scientific workflows (i.e., from myExperiment) to understand the user behavior and styles of work in the context of collaborative SWfMSs. In addition to evaluating SciWorCS, the user studies reveal several interesting facts which can significantly contribute in the research domain, as none of the existing methods considered such empirical studies, and rather relied only on computer generated simulated studies for evaluation

Toward an Understanding of Software Code Cloning as a Development Practice

Code cloning is the practice of duplicating existing source code for use elsewhere within a software system. Within the research community, conventional wisdom has asserted that code cloning is generally a bad practice, and that code clones should be removed or refactored where possible. While there is significant anecdotal evidence that code cloning can lead to a variety of maintenance headaches --- such as code bloat, duplication of bugs, and inconsistent bug fixing --- there has been little empirical study on the frequency, severity, and costs of code cloning with respect to software maintenance. This dissertation seeks to improve our understanding of code cloning as a common development practice through the study of several widely adopted, medium-sized open source software systems. We have explored the motivations behind the use of code cloning as a development practice by addressing several fundamental questions: For what reasons do developers choose to clone code? Are there distinct identifiable patterns of cloning? What are the possible short- and long-term term risks of cloning? What management strategies are appropriate for the maintenance and evolution of clones? When is the ``cure'' (refactoring) likely to cause more harm than the ``disease'' (cloning)? There are three major research contributions of this dissertation. First, we propose a set of requirements for an effective clone analysis tool based on our experiences in clone analysis of large software systems. These requirements are demonstrated in an example implementation which we used to perform the case studies prior to and included in this thesis. Second, we present an annotated catalogue of common code cloning patterns that we observed in our studies. Third, we present an empirical study of the relative frequencies and likely harmfulness of instances of these cloning patterns as observed in two medium-sized open source software systems, the Apache web server and the Gnumeric spreadsheet application. In summary, it appears that code cloning is often used as a principled engineering technique for a variety of reasons, and that as many as 71% of the clones in our study could be considered to have a positive impact on the maintainability of the software system. These results suggest that the conventional wisdom that code clones are generally harmful to the quality of a software system has been proven wrong

Towards Semantic Clone Detection, Benchmarking, and Evaluation

Developers copy and paste their code to speed up the development process. Sometimes, they copy code from other systems or look up code online to solve a complex problem. Developers reuse copied code with or without modifications. The resulting similar or identical code fragments are called code clones. Sometimes clones are unintentionally written when a developer implements the same or similar functionality. Even when the resulting code fragments are not textually similar but implement the same functionality they are still considered to be clones and are classified as semantic clones. Semantic clones are defined as code fragments that perform the exact same computation and are implemented using different syntax. Software cloning research indicates that code clones exist in all software systems; on average, 5% to 20% of software code is cloned. Due to the potential impact of clones, whether positive or negative, it is essential to locate, track, and manage clones in the source code. Considerable research has been conducted on all types of code clones, including clone detection, analysis, management, and evaluation. Despite the great interest in code clones, there has been considerably less work conducted on semantic clones. As described in this thesis, I advance the state-of-the-art in semantic clone research in several ways. First, I conducted an empirical study to investigate the status of code cloning in and across open-source game systems and the effectiveness of different normalization, filtering, and transformation techniques for detecting semantic clones. Second, I developed an approach to detect clones across .NET programming languages using an intermediate language. Third, I developed a technique using an intermediate language and an ontology to detect semantic clones. Fourth, I mined Stack Overflow answers to build a semantic code clone benchmark that represents real semantic code clones in four programming languages, C, C#, Java, and Python. Fifth, I defined a comprehensive taxonomy that identifies semantic clone types. Finally, I implemented an injection framework that uses the benchmark to compare and evaluate semantic code clone detectors by automatically measuring recall

Sequencing the potato genome: outline and first results to come from the elucidation of the sequence of the world's third most important food crop

Potato is a member of the Solanaceae, a plant family that includes several other economically important species, such as tomato, eggplant, petunia, tobacco and pepper. The Potato Genome Sequencing Consortium (PGSC) aims to elucidate the complete genome sequence of potato, the third most important food crop in the world. The PGSC is a collaboration between 13 research groups from China, India, Poland, Russia, the Netherlands, Ireland, Argentina, Brazil, Chile, Peru, USA, New Zealand and the UK. The potato genome consists of 12 chromosomes and has a (haploid) length of approximately 840 million base pairs, making it a medium-sized plant genome. The sequencing project builds on a diploid potato genomic bacterial artificial chromosome (BAC) clone library of 78000 clones, which has been fingerprinted and aligned into ~7000 physical map contigs. In addition, the BAC-ends have been sequenced and are publicly available. Approximately 30000 BACs are anchored to the Ultra High Density genetic map of potato, composed of 10000 unique AFLPTM markers. From this integrated genetic-physical map, between 50 to 150 seed BACs have currently been identified for every chromosome. Fluorescent in situ hybridization experiments on selected BAC clones confirm these anchor points. The seed clones provide the starting point for a BAC-by-BAC sequencing strategy. This strategy is being complemented by whole genome shotgun sequencing approaches using both 454 GS FLX and Illumina GA2 instruments. Assembly and annotation of the sequence data will be performed using publicly available and tailor-made tools. The availability of the annotated data will help to characterize germplasm collections based on allelic variance and to assist potato breeders to more fully exploit the genetic potential of potat