miRNAminer: A tool for homologous microRNA gene search

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs), present in most metazoans, are small non-coding RNAs that control gene expression by negatively regulating translation through binding to the 3'UTR of mRNA transcripts. Previously, experimental and computational methods were used to construct miRNA gene repositories agreeing with careful submission guidelines.</p> <p>Results</p> <p>An algorithm we developed – miRNAminer – is used for homologous conserved miRNA gene search in several animal species. Given a search query, candidate homologs from different species are tested for their known miRNA properties, such as secondary structure, energy and alignment and conservation, in order to asses their fidelity. When applying miRNAminer on seven mammalian species we identified several hundreds of high-confidence homologous miRNAs increasing the total collection of (miRbase) miRNAs, in these species, by more than 50%. miRNAminer uses stringent criteria and exhibits high sensitivity and specificity.</p> <p>Conclusion</p> <p>We present – miRNAminer – the first web-server for homologous miRNA gene search in animals. miRNAminer can be used to identify conserved homolog miRNA genes and can also be used prior to depositing miRNAs in public databases. miRNAminer is available at <url>http://pag.csail.mit.edu/mirnaminer</url>.</p

Computational and statistical approaches to analyzing variants identified by exome sequencing

New sequencing technology has enabled the identification of thousands of single nucleotide polymorphisms in the exome, and many computational and statistical approaches to identify disease-association signals have emerged.National Institutes of Health (U.S.) (Grant R01-MH084676)National Institutes of Health (U.S.) (Grant R01-GM078598)National Institutes of Health (U.S.) (Training grant T32-HL07604-25)Brigham and Women's Hospital (Division of Cardiovascular Medicine

Object and Reference Immutability using Java Generics

A compiler-checked immutability guarantee provides useful documentation, facilitates reasoning, and enables optimizations. This paper presents Immutability Generic Java (IGJ), a novel language extension that expresses immutability without changing Javas syntax by building upon Javas generics and annotation mechanisms. In IGJ, each class has one additional generic parameter that is Immutable, Mutable, or ReadOnly. IGJ guarantees both reference immutability (only mutable references can mutate an object) and object immutability (an immutable reference points to an immutable object). IGJ is the first proposal for enforcing object immutability, and its reference immutability is more expressive than previous work. IGJ also permits covariant changes of generic arguments in a type-safe manner, e.g., a readonly list of integers is a subtype of a readonly list of numbers. IGJ extends Javas type system with a few simple rules. We formalize this type system and prove it sound. Our IGJ compiler works by type-erasure and generates byte-code that can be executed on any JVM without runtime penalty

Automatic Creation of SQL Injection and Cross-Site Scripting Attacks

We present a technique for finding security vulnerabilitiesin Web applications. SQL Injection (SQLI) and cross-sitescripting (XSS) attacks are widespread forms of attackin which the attacker crafts the input to the application toaccess or modify user data and execute malicious code. Inthe most serious attacks (called second-order, or persistent,XSS), an attacker can corrupt a database so as to causesubsequent users to execute malicious code.This paper presents an automatic technique for creatinginputs that expose SQLI and XSS vulnerabilities. The techniquegenerates sample inputs, symbolically tracks taintsthrough execution (including through database accesses),and mutates the inputs to produce concrete exploits. Oursis the first analysis of which we are aware that preciselyaddresses second-order XSS attacks.Our technique creates real attack vectors, has few falsepositives, incurs no runtime overhead for the deployed application,works without requiring modification of applicationcode, and handles dynamic programming-languageconstructs. We implemented the technique for PHP, in a toolArdilla. We evaluated Ardilla on five PHP applicationsand found 68 previously unknown vulnerabilities (23 SQLI,33 first-order XSS, and 12 second-order XSS)

Refactoring for parameterizing Java classes

Type safety and expressiveness of many existing Java libraries and theirclient applications would improve, if the libraries were upgraded to definegeneric classes. Efficient and accurate tools exist to assist clientapplications to use generics libraries, but so far the libraries themselvesmust be parameterized manually, which is a tedious, time-consuming, anderror-prone task. We present a type-constraint-based algorithm forconverting non-generic libraries to add type parameters. The algorithmhandles the full Java language and preserves backward compatibility, thusmaking it safe for existing clients. Among other features, it is capableof inferring wildcard types and introducing type parameters formutually-dependent classes. We have implemented the algorithm as a fullyautomatic refactoring in Eclipse.We evaluated our work in two ways. First, our tool parameterized code thatwas lacking type parameters. We contacted the developers of several ofthese applications, and in all cases where we received a response, theyconfirmed that the resulting parameterizations were correct and useful.Second, to better quantify its effectiveness, our tool parameterizedclasses from already-generic libraries, and we compared the results tothose that were created by the libraries' authors. Our tool performed therefactoring accurately -- in 87% of cases the results were as good as thosecreated manually by a human expert, in 9% of cases the tool results werebetter, and in 4% of cases the tool results were worse

HAMPI: A Solver for String Constraints

Many automatic testing, analysis, and verification techniques for programs can be effectively reduced to a constraint-generation phase followed by a constraint-solving phase. This separation of concerns often leads to more effective and maintainable tools. The increasing efficiency of off-the-shelf constraint solvers makes this approach even more compelling. However, there are few, if any, effective and sufficiently expressive off-the-shelf solvers for string constraints generated by analysis techniques for string-manipulating programs. We designed and implemented Hampi, a solver for string constraints over bounded string variables. Hampi constraints express membership in regular languages and bounded context-free languages. Hampi constraints may contain context-free-language definitions, regular-language definitions and operations, and the membership predicate. Given a set of constraints, Hampi outputs a string that satisfies all the constraints, or reports that the constraints are unsatisfiable. Hampi is expressive and efficient, and can be successfully applied to testing and analysis of real programs. Our experiments use Hampi in: static and dynamic analyses for finding SQL injection vulnerabilities in Web applications; automated bug finding in C programs using systematic testing; and compare Hampi with another string solver. Hampi's source code, documentation, and the experimental data are available at http://people.csail.mit.edu/akiezun/hampi

Finding the needles in the haystack: Generating legal test inputs for object-oriented programs

A test input for an object-oriented program typically consists of asequence of method calls that use the API defined by the programunder test. Generating legal test inputs can be challenging because,for some programs, the set of legal method sequences is much smallerthan the set of all possible sequences; without a formalspecification of legal sequences, an input generator is bound toproduce mostly illegal sequences.We propose a scalable technique that combines dynamic analysis withrandom testing to help an input generator create legal test inputswithout a formal specification, even for programs in whichmost sequences are illegal. The technique uses an example executionof the program to infer a model of legal call sequences, and usesthe model to guide a random input generator towards legal butbehaviorally-diverse sequences.We have implemented our technique for Java, in a tool calledPalulu, and evaluated its effectiveness in creating legal inputsfor real programs. Our experimental results indicate that thetechnique is effective and scalable. Our preliminary evaluationindicates that the technique can quickly generate legal sequencesfor complex inputs: in a case study, Palulu created legal testinputs in seconds for a set of complex classes, for which it took anexpert thirty minutes to generate a single legal input

miRviewer: a multispecies microRNA homologous viewer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression via binding to the 3' ends of mRNAs. MiRNAs have been associated with many cellular events ascertaining their central role in gene regulation. In order to better understand miRNAs of interest it is of utmost importance to learn about the genomic conservation of these genes.</p> <p>Findings</p> <p>The miRviewer web-server, presented here, encompasses all known miRNAs of currently fully annotated animal genomes in a visual 'birds-eye' view representation. miRviewer provides a graphical outlook of the current miRNA world together with sequence alignments and secondary structures of each miRNA. As a test case we experimentally examined the expression of several miRNAs in various animals.</p> <p>Conclusions</p> <p>miRviewer completes the homologous miRNA space with hundreds of unreported miRNAs and is available at: <url>http://people.csail.mit.edu/akiezun/miRviewer</url></p