Imputation in admixed populations is an important problem but challenging due to the complex linkage disequilibrium (LD) pattern. The emergence of large reference panels such as that from the 1,000 ...Genomes Project enables more accurate imputation in general, and in particular for admixed populations and for uncommon variants. To efficiently benefit from these large reference panels, one key issue to consider in modern genotype imputation framework is the selection of effective reference panels. In this work, we consider a number of methods for effective reference panel construction inside a hidden Markov model and specific to each target individual. These methods fall into two categories: identity‐by‐state (IBS) based and ancestry‐weighted approach. We evaluated the performance on individuals from recently admixed populations. Our target samples include 8,421 African Americans and 3,587 Hispanic Americans from the Women' Health Initiative, which allow assessment of imputation quality for uncommon variants. Our experiments include both large and small reference panels; large, medium, and small target samples; and in genome regions of varying levels of LD. We also include BEAGLE and IMPUTE2 for comparison. Experiment results with large reference panel suggest that our novel piecewise IBS method yields consistently higher imputation quality than other methods/software. The advantage is particularly noteworthy among uncommon variants where we observe up to 5.1% information gain with the difference being highly significant (Wilcoxon signed rank test P‐value < 0.0001). Our work is the first that considers various sensible approaches for imputation in admixed populations and presents a comprehensive comparison.
Since the publication of the first comprehensive linkage map for the laboratory mouse, the architecture of recombination as a basic biological process has become amenable to investigation in ...mammalian model organisms. Here we take advantage of high-density genotyping and the unique pedigree structure of the incipient Collaborative Cross to investigate the roles of sex and genetic background in mammalian recombination. Our results confirm the observation that map length is longer when measured through female meiosis than through male meiosis, but we find that this difference is modified by genotype at loci on both the X chromosome and the autosomes. In addition, we report a striking concentration of crossovers in the distal ends of autosomes in male meiosis that is absent in female meiosis. The presence of this pattern in both single- and double-recombinant chromosomes, combined with the absence of a corresponding asymmetry in the distribution of double-strand breaks, indicates a regulated sequence of events specific to male meiosis that is anchored by chromosome ends. This pattern is consistent with the timing of chromosome pairing and evolutionary constraints on male recombination. Finally, we identify large regions of reduced crossover frequency that together encompass 5% of the genome. Many of these "cold regions" are enriched for segmental duplications, suggesting an inverse local correlation between recombination rate and mutation rate for large copy number variants.
According to the Taiwan Cancer Report, in 2018, prostate cancer was one of the top five cancers reported in men. Each year, many patients with prostate cancer undergo radical prostatectomy (RP) ...therapy. One of the most common RP complications is erectile dysfunction (ED). Although consensus guidelines for the management of sexual dysfunction after prostate cancer surgery have been developed for many Western and Asian countries, no such clinical practice guidelines have been developed for Taiwan. The consensus opinions expressed in this article were discussed by numerous experienced physicians in Taiwan, based on both existing international guidelines and their individual experiences with clinical trials and providing advice to clinical physicians on how to inform patients of the risk of ED prior to surgery. This review also discusses how recovery and rehabilitation may be affected by socioeconomic status, the existence of an intimate relationship, comorbidities, or the need for cancer adjuvant therapy and how to determine rehabilitation goals and provide appropriate treatments to assist in the recovery of both short- and long-term sexual function.
In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. ...However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
User-managed-events is a popular feature on social networks. Take Facebook Events as an example: over 135 million events were created in 2015 and over 550 million people use events each month. In ...this work, we consider the heavy sparseness in both user and event feedback history caused by short lifespans (transiency) of events and user participation patterns in a production event system. We propose to solve the resulting cold-start problems by introducing a joint representation model to project users and events into the same latent space. Our model based on parallel Convolutional Neural Networks captures semantic meaning in event text and also utilizes heterogeneous user knowledge available in the social network. By feeding the model output as user and event representation into a combiner prediction model, we show that our representation model improves the prediction accuracy over existing techniques (+6% AUC lift). Our method provides a generic way to match heterogeneous information from different domains and applies to a wide range of applications in social networks.
Genotype imputation has become an indispensible step in genome-wide association studies (GWAS). Imputation accuracy, directly influencing downstream analysis, has shown to be improved using ...re-sequencing-based reference panels; however, this comes at the cost of high computational burden due to the huge number of potentially imputable markers (tens of millions) discovered through sequencing a large number of individuals. Therefore, there is an increasing need for access to imputation quality information without actually conducting imputation. To facilitate this process, we have established a publicly available SNP and indel imputability database, aiming to provide direct access to imputation accuracy information for markers identified by the 1000 Genomes Project across four major populations and covering multiple GWAS genotyping platforms.
SNP and indel imputability information can be retrieved through a user-friendly interface by providing the ID(s) of the desired variant(s) or by specifying the desired genomic region. The query results can be refined by selecting relevant GWAS genotyping platform(s). This is the first database providing variant imputability information specific to each continental group and to each genotyping platform. In Filipino individuals from the Cebu Longitudinal Health and Nutrition Survey, our database can achieve an area under the receiver-operating characteristic curve of 0.97, 0.91, 0.88 and 0.79 for markers with minor allele frequency >5%, 3-5%, 1-3% and 0.5-1%, respectively. Specifically, by filtering out 48.6% of markers (corresponding to a reduction of up to 48.6% in computational costs for actual imputation) based on the imputability information in our database, we can remove 77%, 58%, 51% and 42% of the poorly imputed markers at the cost of only 0.3%, 0.8%, 1.5% and 4.6% of the well-imputed markers with minor allele frequency >5%, 3-5%, 1-3% and 0.5-1%, respectively.
http://www.unc.edu/∼yunmli/imputability.html
Genetic imputation has become standard practice in modern genetic studies. However, several important issues have not been adequately addressed including the utility of study‐specific reference, ...performance in admixed populations, and quality for less common (minor allele frequency MAF 0.005–0.05) and rare (MAF < 0.005) variants. These issues only recently became addressable with genome‐wide association studies (GWAS) follow‐up studies using dense genotyping or sequencing in large samples of non‐European individuals. In this work, we constructed a study‐specific reference panel of 3,924 haplotypes using African Americans in the Women's Health Initiative (WHI) genotyped on both the Metabochip and the Affymetrix 6.0 GWAS platform. We used this reference panel to impute into 6,459 WHI SNP Health Association Resource (SHARe) study subjects with only GWAS genotypes. Our analysis confirmed the imputation quality metric Rsq (estimated r2, specific to each SNP) as an effective post‐imputation filter. We recommend different Rsq thresholds for different MAF categories such that the average (across SNPs) Rsq is above the desired dosage r2 (squared Pearson correlation between imputed and experimental genotypes). With a desired dosage r2 of 80%, 99.9% (97.5%, 83.6%, 52.0%, 20.5%) of SNPs with MAF > 0.05 (0.03–0.05, 0.01–0.03, 0.005–0.01, and 0.001–0.005) passed the post‐imputation filter. The average dosage r2 for these SNPs is 94.7%, 92.1%, 89.0%, 83.1%, and 79.7%, respectively. These results suggest that for African Americans imputation of Metabochip SNPs from GWAS data, including low frequency SNPs with MAF 0.005–0.05, is feasible and worthwhile for power increase in downstream association analysis provided a sizable reference panel is available.
Internet complexity makes reasoning about traffic equilibrium difficult, partly because users react to congestion. This difficulty calls for an analytic technique that is simple, yet have enough ...details to capture user behavior and flexibly address a broad range of issues.
This paper presents such a technique. It treats traffic equilibrium as a balance between an inflow controlled by users, and an outflow controlled by the network (link capacity, congestion avoidance, etc.). This decomposition is demonstrated with a surfing session model, and validated with a traffic trace and
NS2 simulations.
The technique’s accessibility and breadth are illustrated through an analysis of several issues concerning the location, stability, robustness and dynamics of traffic equilibrium.
The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred ...CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites-all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits.
Clustering and classification hierarchies are organizational structures of a set of objects. Multiple hierarchies may be derived over the same set of objects, which makes distance computation between ...hierarchies an important task. In this paper, we model the classification and clustering hierarchies as rooted, leaf-labeled, unordered trees. We propose a novel distance metric Split-Order distance to evaluate the organizational structure difference between two hierarchies over the same set of leaf objects. Split-Order distance reflects the order in which subsets of the tree leaves are differentiated from each other and can be used to explain the relationships between the leaf objects. We also propose an efficient algorithm for computing Split-Order distance between two trees in O(n2d4) time, where n is the number of leaves, and d is the maximum number of children of any node. Our experiments on both real and synthetic data demonstrate the efficiency and effectiveness of our algorithm.
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