Spectral imaging in preclinical research and clinical pathology.

Spectral imaging methods are attracting increased interest from researchers and practitioners in basic science, pre-clinical and clinical arenas. A combination of better labeling reagents and better optics creates opportunities to detect and measure multiple parameters at the molecular and cellular level. These tools can provide valuable insights into the basic mechanisms of life, and yield diagnostic and prognostic information for clinical applications. There are many multispectral technologies available, each with its own advantages and limitations. This chapter will present an overview of the rationale for spectral imaging, and discuss the hardware, software and sample labeling strategies that can optimize its usefulness in clinical settings

Visualization and Correction of Automated Segmentation, Tracking and Lineaging from 5-D Stem Cell Image Sequences

Results: We present an application that enables the quantitative analysis of multichannel 5-D (x, y, z, t, channel) and large montage confocal fluorescence microscopy images. The image sequences show stem cells together with blood vessels, enabling quantification of the dynamic behaviors of stem cells in relation to their vascular niche, with applications in developmental and cancer biology. Our application automatically segments, tracks, and lineages the image sequence data and then allows the user to view and edit the results of automated algorithms in a stereoscopic 3-D window while simultaneously viewing the stem cell lineage tree in a 2-D window. Using the GPU to store and render the image sequence data enables a hybrid computational approach. An inference-based approach utilizing user-provided edits to automatically correct related mistakes executes interactively on the system CPU while the GPU handles 3-D visualization tasks. Conclusions: By exploiting commodity computer gaming hardware, we have developed an application that can be run in the laboratory to facilitate rapid iteration through biological experiments. There is a pressing need for visualization and analysis tools for 5-D live cell image data. We combine accurate unsupervised processes with an intuitive visualization of the results. Our validation interface allows for each data set to be corrected to 100% accuracy, ensuring that downstream data analysis is accurate and verifiable. Our tool is the first to combine all of these aspects, leveraging the synergies obtained by utilizing validation information from stereo visualization to improve the low level image processing tasks.Comment: BioVis 2014 conferenc

metaSHARK: software for automated metabolic network prediction from DNA sequence and its application to the genomes of Plasmodium falciparum and Eimeria tenella

The metabolic SearcH And Reconstruction Kit (metaSHARK) is a new fully automated software package for the detection of enzyme-encoding genes within unannotated genome data and their visualization in the context of the surrounding metabolic network. The gene detection package (SHARKhunt) runs on a Linux systemand requires only a set of raw DNA sequences (genomic, expressed sequence tag and/ or genome survey sequence) as input. Its output may be uploaded to our web-based visualization tool (SHARKview) for exploring and comparing data from different organisms. We first demonstrate the utility of the software by comparing its results for the raw Plasmodium falciparum genome with the manual annotations available at the PlasmoDB and PlasmoCyc websites. We then apply SHARKhunt to the unannotated genome sequences of the coccidian parasite Eimeria tenella and observe that, at an E-value cut-off of 10(-20), our software makes 142 additional assertions of enzymatic function compared with a recent annotation package working with translated open reading frame sequences. The ability of the software to cope with low levels of sequence coverage is investigated by analyzing assemblies of the E.tenella genome at estimated coverages from 0.5x to 7.5x. Lastly, as an example of how metaSHARK can be used to evaluate the genomic evidence for specific metabolic pathways, we present a study of coenzyme A biosynthesis in P.falciparum and E.tenella

The 'who' and 'what' of #diabetes on Twitter

Social media are being increasingly used for health promotion, yet the landscape of users, messages and interactions in such fora is poorly understood. Studies of social media and diabetes have focused mostly on patients, or public agencies addressing it, but have not looked broadly at all the participants or the diversity of content they contribute. We study Twitter conversations about diabetes through the systematic analysis of 2.5 million tweets collected over 8 months and the interactions between their authors. We address three questions: (1) what themes arise in these tweets?, (2) who are the most influential users?, (3) which type of users contribute to which themes? We answer these questions using a mixed-methods approach, integrating techniques from anthropology, network science and information retrieval such as thematic coding, temporal network analysis, and community and topic detection. Diabetes-related tweets fall within broad thematic groups: health information, news, social interaction, and commercial. At the same time, humorous messages and references to popular culture appear consistently, more than any other type of tweet. We classify authors according to their temporal 'hub' and 'authority' scores. Whereas the hub landscape is diffuse and fluid over time, top authorities are highly persistent across time and comprise bloggers, advocacy groups and NGOs related to diabetes, as well as for-profit entities without specific diabetes expertise. Top authorities fall into seven interest communities as derived from their Twitter follower network. Our findings have implications for public health professionals and policy makers who seek to use social media as an engagement tool and to inform policy design.Comment: 25 pages, 11 figures, 7 tables. Supplemental spreadsheet available from http://journals.sagepub.com/doi/suppl/10.1177/2055207616688841, Digital Health, Vol 3, 201

Digital Pharmacovigilance: the medwatcher system for monitoring adverse events through automated processing of internet social media and crowdsourcing

Thesis (Ph.D.)--Boston UniversityHalf of Americans take a prescription drug, medical devices are in broad use, and population coverage for many vaccines is over 90%. Nearly all medical products carry risk of adverse events (AEs), sometimes severe. However, pre- approval trials use small populations and exclude participants by specific criteria, making them insufficient to determine the risks of a product as used in the population. Existing post-marketing reporting systems are critical, but suffer from underreporting. Meanwhile, recent years have seen an explosion in adoption of Internet services and smartphones. MedWatcher is a new system that harnesses emerging technologies for pharmacovigilance in the general population. MedWatcher consists of two components, a text-processing module, MedWatcher Social, and a crowdsourcing module, MedWatcher Personal. With the natural language processing component, we acquire public data from the Internet, apply classification algorithms, and extract AE signals. With the crowdsourcing application, we provide software allowing consumers to submit AE reports directly. Our MedWatcher Social algorithm for identifying symptoms performs with 77% precision and 88% recall on a sample of Twitter posts. Our machine learning algorithm for identifying AE-related posts performs with 68% precision and 89% recall on a labeled Twitter corpus. For zolpidem tartrate, certolizumab pegol, and dimethyl fumarate, we compared AE profiles from Twitter with reports from the FDA spontaneous reporting system. We find some concordance (Spearman's rho= 0.85, 0.77, 0.82, respectively, for symptoms at MedDRA System Organ Class level). Where the sources differ, milder effects are overrepresented in Twitter. We also compared post-marketing profiles with trial results and found little concordance. MedWatcher Personal saw substantial user adoption, receiving 550 AE reports in a one-year period, including over 400 for one device, Essure. We categorized 400 Essure reports by symptom, compared them to 129 reports from the FDA spontaneous reporting system, and found high concordance (rho = 0.65) using MedDRA Preferred Term granularity. We also compared Essure Twitter posts with MedWatcher and FDA reports, and found rho= 0.25 and 0.31 respectively. MedWatcher represents a novel pharmacoepidemiology surveillance informatics system; our analysis is the first to compare AEs across social media, direct reporting, FDA spontaneous reports, and pre-approval trials