Methodological Issues in Multistage Genome-Wide Association Studies

Because of the high cost of commercial genotyping chip technologies, many investigations have used a two-stage design for genome-wide association studies, using part of the sample for an initial discovery of ``promising'' SNPs at a less stringent significance level and the remainder in a joint analysis of just these SNPs using custom genotyping. Typical cost savings of about 50% are possible with this design to obtain comparable levels of overall type I error and power by using about half the sample for stage I and carrying about 0.1% of SNPs forward to the second stage, the optimal design depending primarily upon the ratio of costs per genotype for stages I and II. However, with the rapidly declining costs of the commercial panels, the generally low observed ORs of current studies, and many studies aiming to test multiple hypotheses and multiple endpoints, many investigators are abandoning the two-stage design in favor of simply genotyping all available subjects using a standard high-density panel. Concern is sometimes raised about the absence of a ``replication'' panel in this approach, as required by some high-profile journals, but it must be appreciated that the two-stage design is not a discovery/replication design but simply a more efficient design for discovery using a joint analysis of the data from both stages. Once a subset of highly-significant associations has been discovered, a truly independent ``exact replication'' study is needed in a similar population of the same promising SNPs using similar methods.Comment: Published in at http://dx.doi.org/10.1214/09-STS288 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Survey of Physical Layer Security Techniques for 5G Wireless Networks and Challenges Ahead

Physical layer security which safeguards data confidentiality based on the information-theoretic approaches has received significant research interest recently. The key idea behind physical layer security is to utilize the intrinsic randomness of the transmission channel to guarantee the security in physical layer. The evolution towards 5G wireless communications poses new challenges for physical layer security research. This paper provides a latest survey of the physical layer security research on various promising 5G technologies, including physical layer security coding, massive multiple-input multiple-output, millimeter wave communications, heterogeneous networks, non-orthogonal multiple access, full duplex technology, etc. Technical challenges which remain unresolved at the time of writing are summarized and the future trends of physical layer security in 5G and beyond are discussed.Comment: To appear in IEEE Journal on Selected Areas in Communication

The Effectiveness of <i>t</i>-Way Test Data Generation

Modern society is increasingly dependent on the correct functioning of software and increasingly so in areas that are considered safety related or safety critical. Therefore, there is an increasing need to be able to verify and validate that the software is in fact correct and will perform its intended function. Many approaches to this problem have been proposed; however, none seems likely to supplant the role of testing in the near future. If we accept that there is, and will be, a continuing need to be able to test software then the question becomes one of how can this be done effectively, both in terms of ability to detect errors and in terms of cost. One avenue of research that offers prospects of improving both of these aspects is the automatic generation of test data. There has recently been a large amount of work conducted in this area. One particularly promising direction has been the application of ideas from the field of experimental design and in particular, the field of t-way adequate factorial designs. The area however, is not without issues; there is evidence that the technique is capable of detecting errors but that evidence is not unequivocal. Moreover, as with almost all work in the area of automatic test generation, there has been very little comparative work comparing the technique with other test data generation techniques. Worse, there has been effectively no work done that compares any automatic test data generation technique with the effectiveness of tests generated by humans. Another major issue with the technique is the number of tests that applying the technique can result in. This implies that there is a need for an automated oracle if the technique is to be successfully applied. The flaw with this is of course that in most situations the oracle is the human that is conducting the tests, a point often ignored in testing research. The work presented here addresses both of these points. To do this I have used a code base taken from an industrial engine control system that has an existing set of high quality unit tests developed by hand. To complement this, several other techniques for automatically generating test data have been applied, namely random testing, random experimental designs and a technique for generating single factor experiments. To address the issue of being able to compare the error detection ability of all of the sets of test vectors, rather than the usual effectiveness surrogates of code coverage I have used mutation analysis on the code base to directly measure the ability of each set of test vectors to discover common coding errors. The results presented here show that test data generation techniques based on t-way factorial designs are at least as effective as handgenerated tests and superior to random testing and the factor experimental technique. The oracle problem associated with the factorial design techniques was addressed using a test set minimisation approach. The mutation tool monitored which vectors could “kill” which code mutants. After a subset of the test vectors had been run, the most effective vectors were retained and the rest discarded. Likewise, mutants that were killed were removed from further consideration and the process repeated. Experimental results show that this minimisation procedure is effective at reducing computational overhead and is capable of producing final sets of test vectors that are comparable in size with the sets of hand-generated tests and so amenable to final hand checking

Metamodel Instance Generation: A systematic literature review

Modelling and thus metamodelling have become increasingly important in Software Engineering through the use of Model Driven Engineering. In this paper we present a systematic literature review of instance generation techniques for metamodels, i.e. the process of automatically generating models from a given metamodel. We start by presenting a set of research questions that our review is intended to answer. We then identify the main topics that are related to metamodel instance generation techniques, and use these to initiate our literature search. This search resulted in the identification of 34 key papers in the area, and each of these is reviewed here and discussed in detail. The outcome is that we are able to identify a knowledge gap in this field, and we offer suggestions as to some potential directions for future research.Comment: 25 page

A design for testability study on a high performance automatic gain control circuit.

A comprehensive testability study on a commercial automatic gain control circuit is presented which aims to identify design for testability (DfT) modifications to both reduce production test cost and improve test quality. A fault simulation strategy based on layout extracted faults has been used to support the study. The paper proposes a number of DfT modifications at the layout, schematic and system levels together with testability. Guidelines that may well have generic applicability. Proposals for using the modifications to achieve partial self test are made and estimates of achieved fault coverage and quality levels presente

Multi-class protein fold classification using a new ensemble machine learning approach.

Protein structure classification represents an important process in understanding the associations between sequence and structure as well as possible functional and evolutionary relationships. Recent structural genomics initiatives and other high-throughput experiments have populated the biological databases at a rapid pace. The amount of structural data has made traditional methods such as manual inspection of the protein structure become impossible. Machine learning has been widely applied to bioinformatics and has gained a lot of success in this research area. This work proposes a novel ensemble machine learning method that improves the coverage of the classifiers under the multi-class imbalanced sample sets by integrating knowledge induced from different base classifiers, and we illustrate this idea in classifying multi-class SCOP protein fold data. We have compared our approach with PART and show that our method improves the sensitivity of the classifier in protein fold classification. Furthermore, we have extended this method to learning over multiple data types, preserving the independence of their corresponding data sources, and show that our new approach performs at least as well as the traditional technique over a single joined data source. These experimental results are encouraging, and can be applied to other bioinformatics problems similarly characterised by multi-class imbalanced data sets held in multiple data sources