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  • Oxford University Press (OUP)  (3)
  • 1
    In: JAMIA Open, Oxford University Press (OUP), Vol. 2, No. 3 ( 2019-10-01), p. 353-359
    Abstract: To provide an open-source software package for determining temporal correlations between disease states using longitudinal electronic medical records (EMR). Materials and Methods We have developed an R-based package, Disease Correlation Network (DCN), which builds retrospective matched cohorts from longitudinal medical records to assess for significant temporal correlations between diseases using two independent methodologies: Cox proportional hazards regression and random forest survival analysis. This optimizable package has the potential to control for relevant confounding factors such as age, gender, and other demographic and medical characteristics. Output is presented as a DCN which may be analyzed using a JavaScript-based interactive visualization tool for users to explore statistically significant correlations between disease states of interest using graph-theory-based network topology. Results We have applied this package to a longitudinal dataset at Loyola University Chicago Medical Center with 654 084 distinct initial diagnoses of 51 conditions in 175 539 patients. Over 90% of disease correlations identified are supported by literature review. DCN is available for download at https://github.com/qunfengdong/DCN. Conclusions DCN allows screening of EMR data to identify potential relationships between chronic disease states. This data may then be used to formulate novel research hypotheses for further characterization of these relationships.
    Type of Medium: Online Resource
    ISSN: 2574-2531
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2940623-7
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  • 2
    In: PNAS Nexus, Oxford University Press (OUP), Vol. 1, No. 5 ( 2022-11-01)
    Abstract: Pathogens can elicit high selective pressure on hosts, potentially altering genetic diversity over short evolutionary timescales. Intraspecific variation in immune response is observable as variable survivability from specific infections. The great gerbil (Rhombomys opimus) is a rodent plague host with a heterogenic but highly resistant phenotype. Here, we investigate the genomic basis for plague-resistant phenotypes by exposing wild-caught great gerbils to plague (Yersinia pestis). Whole genome sequencing of 10 survivors and 10 moribund individuals revealed a subset of genomic regions showing elevated differentiation. Gene ontology analysis of candidate genes in these regions demonstrated enrichment of genes directly involved in immune functions, cellular metabolism and the regulation of apoptosis as well as pathways involved in transcription, translation, and gene regulation. Transcriptomic analysis revealed that the early activated great gerbil immune response to plague consisted of classical components of the innate immune system. Our approach combining challenge experiments with transcriptomics and population level sequencing, provides new insight into the genetic background of plague-resistance and confirms its complex nature, most likely involving multiple genes and pathways of both the immune system and regulation of basic cellular functions.
    Type of Medium: Online Resource
    ISSN: 2752-6542
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3120703-0
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  GigaScience Vol. 10, No. 2 ( 2021-01-29)
    In: GigaScience, Oxford University Press (OUP), Vol. 10, No. 2 ( 2021-01-29)
    Abstract: Trillions of microbes inhabit the human body and have a profound effect on human health. The recent development of metagenome-wide association studies and other quantitative analysis methods accelerate the discovery of the associations between human microbiome and diseases. To assess the strengths and limitations of these analytical tools, simulating realistic microbiome datasets is critically important. However, simulating the real microbiome data is challenging because it is difficult to model their correlation structure using explicit statistical models. Results To address the challenge of simulating realistic microbiome data, we designed a novel simulation framework termed MB-GAN, by using a generative adversarial network (GAN) and utilizing methodology advancements from the deep learning community. MB-GAN can automatically learn from given microbial abundances and compute simulated abundances that are indistinguishable from them. In practice, MB-GAN showed the following advantages. First, MB-GAN avoids explicit statistical modeling assumptions, and it only requires real datasets as inputs. Second, unlike the traditional GANs, MB-GAN is easily applicable and can converge efficiently. Conclusions By applying MB-GAN to a case-control gut microbiome study of 396 samples, we demonstrated that the simulated data and the original data had similar first-order and second-order properties, including sparsity, diversities, and taxa-taxa correlations. These advantages are suitable for further microbiome methodology development where high-fidelity microbiome data are needed.
    Type of Medium: Online Resource
    ISSN: 2047-217X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2708999-X
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