Biology subjects

Su, A. I.

Publications and source records attributed to Su, A. I..

10 recordsLinked to original sources

bioRxiv2018

Triflic acid treatment enables LC-MS/MS analysis of insoluble bacterial biomass

The lysis and extraction of soluble bacterial proteins from cells is a common practice for proteomics analyses, but insoluble bacterial biomasses are often left behind. Here, we show that with triflic acid treatment, the insoluble bacterial biomass of Gram- and Gram+ bacteria can be rendered soluble. We use LC-MS/MS shotgun proteomics to show that bacterial proteins in the soluble and insoluble post-lysis fractions differ significantly. Additionally, in the case of Gram- Pseudomonas aeruginosa, triflic acid treatment enables the enrichment of cell envelope-associated proteins. Finally, we apply triflic acid to a human microbiome sample to show that this treatment is robust and enables the identification of a new, complementary subset of proteins from a complex microbial mixture.

systems biology↗

bioRxiv2018

Aligning interests: Integrating Citizen Science Efforts into Schools Through Service Requirements.

Citizen science is an increasingly valuable tool for both scientists and educators. For researchers, citizen science is a means of more quickly investigating questions which would otherwise be time-consuming and costly to study. For educators, citizen science offers a means to engage students in actual research and improve learning outcomes. Since most citizen science projects are usually designed with research goals in mind, many lack the necessary educator materials for successful integration in a formal science education (FSE) setting. In an ideal world, researchers and educators would build the necessary materials together; however, many researchers lack the time, resources, and networks to create these materials early on in the life of a citizen science project. For resource-poor projects, we propose an intermediate entry point for recruiting from the educational setting: community service or service learning requirements (CSSLRs). Many schools require students to participate in community service or service learning activities in order to graduate. When implemented well, CSSLRs provide students with growth and development opportunities outside the classroom while contributing to the community and other worthwhile causes. However, CSSLRs take time, resources, and effort to implement well. Just as citizen science projects need to establish relationships to transition well into formal science education, schools need to cultivate relationships with community service organizations. Students and educators at schools with CSSLRs where implementation is still a work in progress may be left with a burdensome requirement and inadequate support. With the help of a volunteer fulfilling a CSSLR, we investigated the number of students impacted by CSSLRs set at different levels of government and explored the qualifications needed for citizen science projects to fulfill CSSLRs by examining the explicitly-stated justifications for having CSSLRs, surveying how CSSLRs are verified, and using these qualifications to demonstrate how an online citizen science project, Mark2Cure, could use this information to meet the needs of students fulfilling CSSLRs.

scientific communication and education↗

bioRxiv2018

The Healthy Pregnancy Research Program: Transforming Pregnancy Research Through a ResearchKit App

Although maternal morbidity and mortality in the U.S. is among the worst of developed countries, pregnant women have been under-represented in research studies, resulting in deficiencies in evidence-based guidance for treatment. There are over two billion smartphone users worldwide, enabling researchers to easily and cheaply conduct extremely large-scale research studies through smartphone apps, especially among pregnant women in whom app use is exceptionally high, predominantly as an information conduit. We developed the first pregnancy research app that is embedded within an existing, popular pregnancy app for self-management and education of expectant mothers. Through the large-scale and simplified collection of survey and sensor generated data via the app, we aim to improve our understanding of factors that promote a healthy pregnancy for both the mother and developing fetus. From the launch of this cohort study on March 16, 2017 through December 17, 2017, we have enrolled 2,058 pregnant women from all 50 states. Our study population is diverse geographically and demographically, and fairly representative of U.S. population averages. We have collected 14,045 individual surveys and 11,669 days of sleep, activity, blood pressure and heart rate measurements during this time. On average, women stayed engaged in the study for 59 days and 45 percent who reached their due date filled out the final outcome survey. During the first nine months, we demonstrated the potential for a smartphone-based research platform to capture an ever-expanding array of longitudinal, objective and subjective participant-generated data from a continuously growing and diverse population of pregnant women.\n\nFundingSupported in part by the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences grant UL1TR001114 and a grant from the Qualcomm Foundation.

epidemiology↗

bioRxiv2017

Metaproteomics of colonic microbiota unveils discrete protein functions among colitic mice and control groups

Metaproteomics can greatly assist established high-throughput sequencing methodologies to provide systems biological insights into the alterations of microbial protein functionalities correlated with disease-associated dysbiosis of the intestinal microbiota. Here, we utilized the well-characterized murine T cell transfer model of colitis to find specific changes within the intestinal luminal proteome associated with inflammation. MS proteomic analysis of colonic samples permitted the identification of {bsim}10,000-12,000 unique peptides that corresponded to 5,610 protein clusters identified across three groups, including the colitic Rag1-/- T cell recipients, isogenic Rag1-/- controls, and wild-type mice. We demonstrate that the colitic mice exhibited a significant increase in Proteobacteria and Verrucomicrobia and show that such alterations in the microbial communities contributed to the enrichment of specific proteins with transcription and translation gene ontology terms. In combination with 16S sequencing, our metaproteomics-based microbiome studies provide a foundation for assessing alterations in intestinal luminal protein functionalities in a robust and well-characterized mouse model of colitis, and set the stage for future studies to further explore the functional mechanisms of altered protein functionalities associated with dysbiosis and inflammation.\n\nStatement of significance of the studyThe commensal gut microbiota is essential to maintaining health and has a primary role in digestion/metabolism, homeostasis, and protection from pathogenic bacteria. High-throughput sequencing has established Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria as the four major bacterial phyla that comprise the ecological makeup of the intestinal microbiota. However, the tremendous inter-/intra-variability in microbial composition across individuals, as well as along the length of the intestinal tract has made it difficult to definitively ascertain specific bacterial species associated with health or as drivers of disease states, including inflammatory bowel disease. In this study, we expanded upon the current metaproteomics techniques and use the robust and highly reproducible murine T cell transfer model of colitis as well as a comprehensive database of mouse, human, plant, and all microbial genomes sequenced to date to elucidate alterations in both host and gut microbial proteins associated with intestinal inflammation. Our results show that host genetics, gut microbiota, and inflammation have tremendous influences on the intestinal luminal proteomic landscape.

bioinformatics↗

bioRxiv2017

Exploring Applications of Crowdsourcing to Cryo-EM

Extraction of particles from cryo-electron microscopy (cryo-EM) micrographs is a crucial step in processing single-particle datasets. Although algorithms have been developed for automatic particle picking, these algorithms generally rely on two-dimensional templates for particle identification, which may exhibit biases that can propagate artifacts through the reconstruction pipeline. Manual picking is viewed as a gold-standard solution for particle selection, but it is too time-consuming to perform on data sets of thousands of images. In recent years, crowdsourcing has proven effective at leveraging the open web to manually curate datasets. In particular, citizen science projects such as Galaxy Zoo have shown the power of appealing to users' scientific interests to process enormous amounts of data. To this end, we explored the possible applications of crowdsourcing in cryo-EM particle picking, presenting a variety of novel experiments including the production of a fully annotated particle set from untrained citizen scientists. We show the possibilities and limitations of crowdsourcing particle selection tasks, and explore further options for crowdsourcing cryo-EM data processing.

bioinformatics↗

bioRxiv2017

Cross-linking BioThings APIs through JSON-LD to facilitate knowledge exploration

BackgroundApplication Programming Interfaces (APIs) are now widely used to distribute biological data. And many popular biological APIs developed by many different research teams have adopted Javascript Object Notation (JSON) as their primary data format. While usage of a common data format offers significant advantages, that alone is not sufficient for rich integrative queries across APIs.\n\nResultsHere, we have implemented JSON for Linking Data (JSON-LD) technology on the BioThings APIs that we have developed, MyGene.info, MyVariant.info and MyChem.info. JSON-LD provides a standard way to add semantic context to the existing JSON data structure, for the purpose of enhancing the interoperability between APIs. We demonstrated several use cases that were facilitated by semantic annotations using JSON-LD, including simpler and more precise query capabilities as well as API cross-linking.\n\nConclusionsWe believe that this pattern offers a generalizable solution for interoperability of APIs in the life sciences.

bioinformatics↗

bioRxiv2017

Science Game Lab: tool for the unification of biomedical games with a purpose

Games with a purpose and other kinds of citizen science initiatives demonstrate great potential for advancing biomedical science and improving STEM education. Articles documenting the success of projects such as Fold.it and Eyewire in high impact journals have raised wide interest in new applications of the distributed human intelligence that these systems have tapped into. However, the path from a good idea to a successful citizen science game remains highly challenging. Apart from the scientific difficulties of identifying suitable problems and appropriate human-powered solutions, the games still need to be created, need to be fun, and need to reach a large audience that remain engaged for the long-term. Here, we describe Science Game Lab (SGL) (https://sciencegamelab.org), a platform for bootstrapping the production, facilitating the publication, and boosting both the fun and the value of the user experience for scientific games with a purpose.

bioinformatics↗

bioRxiv2017

Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection

Hereditary xerocytosis (HX) is thought to be a rare genetic condition characterized by red blood cell (RBC) dehydration with mild hemolysis. Gain-of-function (GOF) mutations in mechanosensitive Piezo1 ion channels are identified in HX patients. RBC dehydration is linked to reduced Plasmodium infection rates in vitro. We engineered a Piezo1 mouse model of HX and show that Plasmodium infection fails to cause experimental cerebral malaria in these mice. Furthermore, we identified a novel GOF human Piezo1 variant, E756del, present in a third of African population. Remarkably, RBCs from individuals carrying this allele are dehydrated and protected against Plasmodium infection in vitro. The presence of an HX-causing Piezo1 mutation at such high frequencies in African population is surprising, and suggests an association with malaria resistance.

physiology↗

bioRxiv2017

EXPLANe: An Extensible Framework for Poster Annotation with Mobile Devices

SummaryScientific posters tend to be brief, unstructured, and generally unsuitable for communication beyond a poster session. This paper describes EXPLANe, a framework for annotating posters using optical text recognition and web services on mobile devices. EXPLANe is demonstrated through an interface to the MyVariant.info variant annotation web services, and provides users a list of biological information linked with genetic variants (as found via extracted RSIDs from annotated posters). This paper delineates the architecture of the application, and includes results of a five-part evaluation we conducted. Researchers and developers can use the existing codebase as a foundation from which to generate their own annotation tabs when analyzing and annotating posters.\n\nAvailabilityAlpha EXPLANe software is available as an open source application at https://github.com/ngopal/EXPLANe\n\nContactSean D. Mooney (sdmooney@uw.edu)

scientific communication and education↗

bioRxiv2017

A Genome-wide Survey of Mutations in the Jurkat Cell Line

The Jurkat cell line has an extensive history as a model of T cell signaling. But at the turn of the 21st century, some irregularities were observed in Jurkats expression of central regulators of T cell receptor signaling, which raised doubts about how closely the cell line paralleled normal human T cells. While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects. Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing. With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects. We confirm the majority of documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line. This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.

genomics↗