Query Variants Research Articles

A Relative Information Gain-based Query Performance Prediction Framework with Generated Query Variants

Query performance prediction (QPP) methods, which aim to predict the performance of a query, often rely on evidences in the form of different characteristic patterns in the distribution of Retrieval Status Values (RSVs). However, for neural IR models, it is usually observed that the RSVs are often less reliable for QPP because they are bounded within short intervals, different from the situation for statistical models. To address this limitation, we propose a model-agnostic QPP framework that gathers additional evidences by leveraging information from the characteristic patterns of RSV distributions computed over a set of automatically generated query variants, relative to that of the current query. Specifically, the idea behind our proposed method—Weighted Relative Information Gain (WRIG), is that a substantial relative decrease or increase in the standard deviation of the RSVs of the query variants is likely to be a relative indicator of how easy or difficult the original query is. To cater for the absence of human-annotated query variants in real-world scenarios, we further propose an automatic query variant generation method. This can produce variants in a controlled manner by substituting terms from the original query with new ones sampled from a weighted distribution, constructed either via a relevance model or with the help of an embedded representation of query terms. Our experiments on the TREC-Robust, ClueWeb09B, and MS MARCO datasets show that WRIG, by the use of this relative changes in QPP estimate, leads to significantly better results than a state-of-the-art baseline method that leverages information from (manually created) query variants by the application of additive smoothing [ 64 ]. The results also show that our approach can improve the QPP effectiveness of neural retrieval approaches in particular.

VPatho: a deep learning-based two-stage approach for accurate prediction of gain-of-function and loss-of-function variants.

Determining the pathogenicity and functional impact (i.e. gain-of-function; GOF or loss-of-function; LOF) of a variant is vital for unraveling the genetic level mechanisms of human diseases. To provide a 'one-stop' framework for the accurate identification of pathogenicity and functional impact of variants, we developed a two-stage deep-learning-based computational solution, termed VPatho, which was trained using a total of 9619 pathogenic GOF/LOF and 138 026 neutral variants curated from various databases. A total number of 138 variant-level, 262 protein-level and 103 genome-level features were extracted for constructing the models of VPatho. The development of VPatho consists of two stages: (i) a random under-sampling multi-scale residual neural network (ResNet) with a newly defined weighted-loss function (RUS-Wg-MSResNet) was proposed to predict variants' pathogenicity on the gnomAD_NV + GOF/LOF dataset; and (ii) an XGBOD model was constructed to predict the functional impact of the given variants. Benchmarking experiments demonstrated that RUS-Wg-MSResNet achieved the highest prediction performance with the weights calculated based on the ratios of neutral versus pathogenic variants. Independent tests showed that both RUS-Wg-MSResNet and XGBOD achieved outstanding performance. Moreover, assessed using variants from the CAGI6 competition, RUS-Wg-MSResNet achieved superior performance compared to state-of-the-art predictors. The fine-trained XGBOD models were further used to blind test the whole LOF data downloaded from gnomAD and accordingly, we identified 31 nonLOF variants that were previously labeled as LOF/uncertain variants. As an implementation of the developed approach, a webserver of VPatho is made publicly available at http://csbio.njust.edu.cn/bioinf/vpatho/ to facilitate community-wide efforts for profiling and prioritizing the query variants with respect to their pathogenicity and functional impact.

The LDBC Social Network Benchmark

The Social Network Benchmark's Business Intelligence workload (SNB BI) is a comprehensive graph OLAP benchmark targeting analytical data systems capable of supporting graph workloads. This paper marks the finalization of almost a decade of research in academia and industry via the Linked Data Benchmark Council (LDBC). SNB BI advances the state-of-the art in synthetic and scalable analytical database benchmarks in many aspects. Its base is a sophisticated data generator, implemented on a scalable distributed infrastructure, that produces a social graph with small-world phenomena, whose value properties follow skewed and correlated distributions and where values correlate with structure. This is a temporal graph where all nodes and edges follow lifespan-based rules with temporal skew enabling realistic and consistent temporal inserts and (recursive) deletes. The query workload exploiting this skew and correlation is based on LDBC's "choke point"-driven design methodology and will entice technical and scientific improvements in future (graph) database systems. SNB BI includes the first adoption of "parameter curation" in an analytical benchmark, a technique that ensures stable runtimes of query variants across different parameter values. Two performance metrics characterize peak single-query performance (power) and sustained concurrent query throughput. To demonstrate the portability of the benchmark, we present experimental results on a relational and a graph DBMS. Note that these do not constitute an official LDBC Benchmark Result - only audited results can use this trademarked term.

Efficient privacy-preserving whole-genome variant queries.

MotivationDiagnosis and treatment decisions on genomic data have become widespread as the cost of genome sequencing decreases gradually. In this context, disease–gene association studies are of great importance. However, genomic data are very sensitive when compared to other data types and contains information about individuals and their relatives. Many studies have shown that this information can be obtained from the query-response pairs on genomic databases. In this work, we propose a method that uses secure multi-party computation to query genomic databases in a privacy-protected manner. The proposed solution privately outsources genomic data from arbitrarily many sources to the two non-colluding proxies and allows genomic databases to be safely stored in semi-honest cloud environments. It provides data privacy, query privacy and output privacy by using XOR-based sharing and unlike previous solutions, it allows queries to run efficiently on hundreds of thousands of genomic data.ResultsWe measure the performance of our solution with parameters similar to real-world applications. It is possible to query a genomic database with 3 000 000 variants with five genomic query predicates under 400 ms. Querying 1 048 576 genomes, each containing 1 000 000 variants, for the presence of five different query variants can be achieved approximately in 6 min with a small amount of dedicated hardware and connectivity. These execution times are in the right range to enable real-world applications in medical research and healthcare. Unlike previous studies, it is possible to query multiple databases with response times fast enough for practical application. To the best of our knowledge, this is the first solution that provides this performance for querying large-scale genomic data.Availability and implementation https://gitlab.com/DIFUTURE/privacy-preserving-variant-queries.Supplementary information Supplementary data are available at Bioinformatics online.

LDexpress: an online tool for integrating population-specific linkage disequilibrium patterns with tissue-specific expression data

Genome-wide association studies have identified thousands of genetic susceptibility loci associated with cancer as well as other traits and diseases. Mapping germline variation in identified genetic susceptibility regions to alterations in nearby gene expression nominates candidate genes potentially related to disease risk for further functional investigation. We developed LDexpress as an online resource that integrates population-specific linkage disequilibrium data from the 1000 Genomes (1000G) project and tissue-specific expression data from the Genotype-Tissue Expression project to better study regional germline variation impacting gene expression. LDexpress is a publicly available web tool designed to be easy to use, flexible to conduct a wide range of variant queries, and quick to efficiently investigate dozens of query variants across multiple tissue types. We demonstrate the utility of LDexpress using example genomic queries and anticipate this tool will accelerate understanding of disease etiology by uncovering associations of regional germline variation to nearby gene expression.

LDtrait: An Online Tool for Identifying Published Phenotype Associations in Linkage Disequilibrium.

Genome-wide association studies (GWAS) have identified thousands of germline susceptibility loci associated with risk for cancer as well as a wide range of other traits and diseases. An interest of many investigators is identifying traits or diseases that share common susceptibility loci. We developed LDtrait (https://ldlink.nci.nih.gov/?tab=ldtrait) as an open access web tool for finding germline variation associated with multiple traits. LDtrait searches the NHGRI-EBI GWAS Catalog to identify susceptibility loci in linkage disequilibrium (LD) with a user-provided list of query variants. Options allow for modifying LD thresholds, calculating LD from a diverse set of reference populations, and downloading annotated variant lists. Results from example query searches highlight the utility of LDtrait in uncovering cross-trait associations for cancer risk and other traits. LDtrait accelerates etiologic understanding of cancer genetics by rapidly identifying genetic similarities with other traits or diseases. SIGNIFICANCE: The new GWAS search tool LDtrait will expedite discovery of shared genetic components underlying seemingly unrelated diseases and may offer novel insights into cancer research.

A view from the side-line

A look into the reasons and the genetics involved, for the future of precision medicine Just over a year ago, I predicted that cardiology would soon be swept up in the march towards precision medicine. While precision medicine is not yet here, neither in cardiology nor any other medical discipline, numerous advances preserve my optimism and bolster my confidence that we will experience a fundamental shift in how we practice cardiology within the next 5 years. Before sharing some observations, a caveat: I am not a precision medicine expert. My main professional focus is research on the molecular mechanisms of cardiac arrhythmias due to ion channel mutations, and my clinical practice is partly dedicated to treating patients with inherited arrhythmias. Thus, I have had a longstanding interest in genetics, the field in which initial advances triggered the precision medicine wave. So, here I offer an interested outsider’s perspective on how we will continue to move towards the golden paradigm of ‘delivering the right drug in the right dose to the right patient at the right time’. It is on the back of rapidly decreasing costs of gene sequencing technologies that precision medicine promises have been made. With next-generation sequencing, we can now easily query variants across many loci (or all variants at all loci, if whole exome or whole-genome sequencing is applied) to uncover genetic differences among patients presenting with otherwise similar phenotypes. Long QT syndrome, once thought to be a single disorder, is now appreciated …

Efficient processing of optimal meeting point queries in Euclidean space and road networks

Finding an optimal meeting point (OMP) for a group of people (or a set of objects) at different locations is an important problem in spatial query processing. There are many real-life applications related to this problem, such as determining the location of a conference venue, deciding the pick-up location of a tourist bus, and planing tactics of artificial intelligence in real-time strategy games. Formally, given a set $$Q$$ Q of query points in a spatial setting $$P$$ P , an OMP query fetches the point $$o\in P$$ o ? P that minimizes a cost function defined over the distances from $$o$$ o to all points in $$Q$$ Q . Since there are infinitely many locations in a given space setting, it is infeasible to examine all of them to find the OMP, and thus, the problem is challenging. In this paper, we study OMP queries in the following two spatial settings which are common in real-life applications: Euclidean space and road networks. In the setting of Euclidean space, we propose a general framework for answering all OMP query variants and also identify the best algorithms for particular types of OMP queries in the literature. In the setting of road networks, we study how to access only part of the road network and examine part of the candidates. Specifically, we explore two pruning techniques, namely Euclidean distance bound and threshold algorithm, which help improve the efficiency of OMP query processing. Extensive experiments are conducted to demonstrate the efficiency of our proposed approaches on both real and synthetic datasets.

SeqWare Query Engine: storing and searching sequence data in the cloud

BackgroundSince the introduction of next-generation DNA sequencers the rapid increase in sequencer throughput, and associated drop in costs, has resulted in more than a dozen human genomes being resequenced over the last few years. These efforts are merely a prelude for a future in which genome resequencing will be commonplace for both biomedical research and clinical applications. The dramatic increase in sequencer output strains all facets of computational infrastructure, especially databases and query interfaces. The advent of cloud computing, and a variety of powerful tools designed to process petascale datasets, provide a compelling solution to these ever increasing demands.ResultsIn this work, we present the SeqWare Query Engine which has been created using modern cloud computing technologies and designed to support databasing information from thousands of genomes. Our backend implementation was built using the highly scalable, NoSQL HBase database from the Hadoop project. We also created a web-based frontend that provides both a programmatic and interactive query interface and integrates with widely used genome browsers and tools. Using the query engine, users can load and query variants (SNVs, indels, translocations, etc) with a rich level of annotations including coverage and functional consequences. As a proof of concept we loaded several whole genome datasets including the U87MG cell line. We also used a glioblastoma multiforme tumor/normal pair to both profile performance and provide an example of using the Hadoop MapReduce framework within the query engine. This software is open source and freely available from the SeqWare project (http://seqware.sourceforge.net).ConclusionsThe SeqWare Query Engine provided an easy way to make the U87MG genome accessible to programmers and non-programmers alike. This enabled a faster and more open exploration of results, quicker tuning of parameters for heuristic variant calling filters, and a common data interface to simplify development of analytical tools. The range of data types supported, the ease of querying and integrating with existing tools, and the robust scalability of the underlying cloud-based technologies make SeqWare Query Engine a nature fit for storing and searching ever-growing genome sequence datasets.

Nearest Surrounder Queries

In this paper, we present a new type of spatial queries called Nearest Surrounder (NS) queries. An NS query determines the nearest polygon-shaped spatial objects (referred to as nearest surrounder objects) and their orientations with respect to a query point from an object set. Besides, we derive two NS query variants, namely, multitier NS (m-NS) queries and angle-constrained NS (ANS) queries. An m-NS query searches multiple layers of NS objects for the same range of angles from a query point. An ANS query searches for NS objects within a specified range of angles. To evaluate NS queries and their variants, we explore angle-based and distance-based bound properties of polygons, and devise two efficient algorithms, namely, Sweep and Ripple, based on R-tree. The algorithms access objects in an order according to their orientations and distances with respect to a given query point, respectively. They are efficient as they can finish a search with one index lookup. Besides, they can progressively deliver a query result. Through empirical studies, we evaluate the proposed algorithms and report their performance for both synthetic and real object sets.