MOTIVATION: In the training of predictive models using high-dimensional genomic data, multiple studies' worth of data are often combined to increase sample size and improve generalizability. A drawback of this approach is that there may be different sets of features measured in each study due to variations in expression measurement platform or technology. It is often common practice to work only with the intersection of features measured in common across all studies, which results in the blind discarding of potentially useful feature information that is measured in individual or subsets of studies. RESULTS: We characterize the loss in predictive performance incurred by using only the intersection of feature information available across all studies when training predictors using gene expression data from microarray and sequencing datasets. We study the properties of linear and polynomial regression for imputing discarded features and demonstrate improvements in the external performance of prediction functions through simulation and in gene expression data collected on breast cancer patients. To improve this process, we propose a pairwise strategy that applies any imputation algorithm to two studies at a time and averages imputed features across pairs. We demonstrate that the pairwise strategy is preferable to first merging all datasets together and imputing any resulting missing features. Finally, we provide insights on which subsets of intersected and study-specific features should be used so that missing-feature imputation best promotes cross-study replicability. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/YujieWuu/Pairwise_imputation. SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.

MOTIVATION: Genomic data are often produced in batches due to practical restrictions, which may lead to unwanted variation in data caused by discrepancies across batches. Such 'batch effects' often have negative impact on downstream biological analysis and need careful consideration. In practice, batch effects are usually addressed by specifically designed software, which merge the data from different batches, then estimate batch effects and remove them from the data. Here, we focus on classification and prediction problems, and propose a different strategy based on ensemble learning. We first develop prediction models within each batch, then integrate them through ensemble weighting methods. RESULTS: We provide a systematic comparison between these two strategies using studies targeting diverse populations infected with tuberculosis. In one study, we simulated increasing levels of heterogeneity across random subsets of the study, which we treat as simulated batches. We then use the two methods to develop a genomic classifier for the binary indicator of disease status. We evaluate the accuracy of prediction in another independent study targeting a different population cohort. We observed that in independent validation, while merging followed by batch adjustment provides better discrimination at low level of heterogeneity, our ensemble learning strategy achieves more robust performance, especially at high severity of batch effects. These observations provide practical guidelines for handling batch effects in the development and evaluation of genomic classifiers. AVAILABILITY AND IMPLEMENTATION: The data underlying this article are available in the article and in its online supplementary material. Processed data is available in the Github repository with implementation code, at https://github.com/zhangyuqing/bea_ensemble. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Accessibility researchers have been studying wayfinding technologies for people with disabilities for decades, typically focusing on solutions within disability populations - for example, technologies to support blind navigation. Yet, we know little about wayfinding needs across disabilities. In this paper, we describe a qualitative interview study examining the urban navigational experiences of 27 people who identified as older adults and/or who had cognitive, visual, hearing, and/or mobility disabilities. We found that many navigation route preferences were shared across disabilities (e.g., desire to avoid carpeted areas), while others diverged or were in tension (e.g., the need to avoid noisy areas while staying near main thoroughfares). To support design for multiple disability groups, we identify four dimensions of navigation preferences - technology, route, assistance, experience - and describe how these might usefully inform design of more universally usable wayfinding technologies.

MOTIVATION: Prior to applying genomic predictors to clinical samples, the genomic data must be properly normalized to ensure that the test set data are comparable to the data upon which the predictor was trained. The most effective normalization methods depend on data from multiple patients. From a biomedical perspective, this implies that predictions for a single patient may change depending on which other patient samples they are normalized with. This test set bias will occur when any cross-sample normalization is used before clinical prediction. RESULTS: We demonstrate that results from existing gene signatures which rely on normalizing test data may be irreproducible when the patient population changes composition or size using a set of curated, publicly available breast cancer microarray experiments. As an alternative, we examine the use of gene signatures that rely on ranks from the data and show why signatures using rank-based features can avoid test set bias while maintaining highly accurate classification, even across platforms. AVAILABILITY AND IMPLEMENTATION: The code, data and instructions necessary to reproduce our entire analysis is available at https://github.com/prpatil/testsetbias.

In this overview to biomedical computing in the cloud, we discussed two primary ways to use the cloud (a single instance or cluster), provided a detailed example using NGS mapping, and highlighted the associated costs. While many users new to the cloud may assume that entry is as straightforward as uploading an application and selecting an instance type and storage options, we illustrated that there is substantial up-front effort required before an application can make full use of the cloud's vast resources. Our intention was to provide a set of best practices and to illustrate how those apply to a typical application pipeline for biomedical informatics, but also general enough for extrapolation to other types of computational problems. Our mapping example was intended to illustrate how to develop a scalable project and not to compare and contrast alignment algorithms for read mapping and genome assembly. Indeed, with a newer aligner such as Bowtie, it is possible to map the entire African genome using one m2.2xlarge instance in 48 hours for a total cost of approximately $48 in computation time. In our example, we were not concerned with data transfer rates, which are heavily influenced by the amount of available bandwidth, connection latency, and network availability. When transferring large amounts of data to the cloud, bandwidth limitations can be a major bottleneck, and in some cases it is more efficient to simply mail a storage device containing the data to AWS (http://aws.amazon.com/importexport/). More information about cloud computing, detailed cost analysis, and security can be found in references.

BACKGROUND: Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. RESULTS: We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. CONCLUSIONS: The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems.