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  1. Article ; Online: A single dose for me, A wealth of protection for us: The public health cost of individualism in the rollout of COVID-19 vaccine.

    Fu, Wei / Wang, Li-San / Chou, Shin-Yi

    Social science & medicine (1982)

    2024  Volume 348, Page(s) 116849

    Abstract: Objective: This study examines whether individualism weakens the effectiveness of the COVID-19 vaccine eligibility expansions in the United States in 2021, and assesses the associated social benefits or costs associated with individualism.: Methods: ... ...

    Abstract Objective: This study examines whether individualism weakens the effectiveness of the COVID-19 vaccine eligibility expansions in the United States in 2021, and assesses the associated social benefits or costs associated with individualism.
    Methods: We construct a county-level composite individualism index as a proxy of culture and the fraction of vaccine eligible population as a proxy of vaccination campaign (mean: 41.34%). We estimate whether the COVID-19 vaccine eligibility policy is less effective in promoting vaccine coverage, reducing in COVID-19 related hospitalization and death using a linear two-way fixed effect model in a sample of 2866 counties for the period between early December 2020 and July 1, 2021. We also test whether individualism shapes people's attitudes towards vaccine using a linear probability model in a sample of 625,308 individuals aged 18-65 (mean age: 43.3; 49% male; 59.1% non-Hispanic white, 19.1% Hispanic, 12% African American; 5.9% Asian) from the Household Pulse Survey.
    Results: The effects of expanded vaccine eligibility are diminished in counties with greater individualism, as evidenced by lower effectiveness in increasing vaccination rates and reducing outpatient doctor visits primarily for COVID-related symptoms and COVID deaths. Moreover, our results show that this cultural influence on attitudes towards vaccine is more pronounced among the less educated, but unrelated to race.
    Conclusion: Assuming an average level of vaccine eligibility policies and an average intensity of individualism across the nation, we calculate that the average social cost associated with an individualistic culture amid the pandemic is approximately $50.044 billion, equivalent to 1.32% of the total U.S. health care spending in 2019. Our paper suggests that strategies to promote public policy compliance should be tailored to accommodate cultural and social contexts.
    MeSH term(s) Humans ; COVID-19 Vaccines/economics ; COVID-19 Vaccines/administration & dosage ; Male ; COVID-19/prevention & control ; COVID-19/epidemiology ; Adult ; United States ; Female ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Public Health ; SARS-CoV-2 ; Individuality
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2024-03-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 4766-1
    ISSN 1873-5347 ; 0037-7856 ; 0277-9536
    ISSN (online) 1873-5347
    ISSN 0037-7856 ; 0277-9536
    DOI 10.1016/j.socscimed.2024.116849
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The role of structural variations in Alzheimer's disease and other neurodegenerative diseases.

    Wang, Hui / Wang, Li-San / Schellenberg, Gerard / Lee, Wan-Ping

    Frontiers in aging neuroscience

    2023  Volume 14, Page(s) 1073905

    Abstract: Dozens of single nucleotide polymorphisms (SNPs) related to Alzheimer's disease (AD) have been discovered by large scale genome-wide association studies (GWASs). However, only a small portion of the genetic component of AD can be explained by SNPs ... ...

    Abstract Dozens of single nucleotide polymorphisms (SNPs) related to Alzheimer's disease (AD) have been discovered by large scale genome-wide association studies (GWASs). However, only a small portion of the genetic component of AD can be explained by SNPs observed from GWAS. Structural variation (SV) can be a major contributor to the missing heritability of AD; while SV in AD remains largely unexplored as the accurate detection of SVs from the widely used array-based and short-read technology are still far from perfect. Here, we briefly summarized the strengths and weaknesses of available SV detection methods. We reviewed the current landscape of SV analysis in AD and SVs that have been found associated with AD. Particularly, the importance of currently less explored SVs, including insertions, inversions, short tandem repeats, and transposable elements in neurodegenerative diseases were highlighted.
    Language English
    Publishing date 2023-02-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2022.1073905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: hipFG: High-throughput harmonization and integration pipeline for functional genomics data.

    Cifello, Jeffrey / Kuksa, Pavel P / Saravanan, Naveensri / Valladares, Otto / Leung, Yuk Yee / Wang, Li-San

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Preparing functional genomic (FG) data with diverse assay types and file formats for integration into analysis workflows that interpret genome-wide association and other studies is a significant and time-consuming challenge. Here we introduce hipFG, an ... ...

    Abstract Preparing functional genomic (FG) data with diverse assay types and file formats for integration into analysis workflows that interpret genome-wide association and other studies is a significant and time-consuming challenge. Here we introduce hipFG, an automatically customized pipeline for efficient and scalable normalization of heterogenous FG data collections into standardized, indexed, rapidly searchable analysis-ready datasets while accounting for FG datatypes (e.g., chromatin interactions, genomic intervals, quantitative trait loci).
    Language English
    Publishing date 2023-04-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.21.537695
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: hipFG: high-throughput harmonization and integration pipeline for functional genomics data.

    Cifello, Jeffrey / Kuksa, Pavel P / Saravanan, Naveensri / Valladares, Otto / Wang, Li-San / Leung, Yuk Yee

    Bioinformatics (Oxford, England)

    2023  Volume 39, Issue 11

    Abstract: Summary: Preparing functional genomic (FG) data with diverse assay types and file formats for integration into analysis workflows that interpret genome-wide association and other studies is a significant and time-consuming challenge. Here we introduce ... ...

    Abstract Summary: Preparing functional genomic (FG) data with diverse assay types and file formats for integration into analysis workflows that interpret genome-wide association and other studies is a significant and time-consuming challenge. Here we introduce hipFG (Harmonization and Integration Pipeline for Functional Genomics), an automatically customized pipeline for efficient and scalable normalization of heterogenous FG data collections into standardized, indexed, rapidly searchable analysis-ready datasets while accounting for FG datatypes (e.g. chromatin interactions, genomic intervals, quantitative trait loci).
    Availability and implementation: hipFG is freely available at https://bitbucket.org/wanglab-upenn/hipFG. A Docker container is available at https://hub.docker.com/r/wanglab/hipfg.
    MeSH term(s) Software ; Genome-Wide Association Study ; Genomics ; Chromatin ; Quantitative Trait Loci
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-12-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btad673
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Omnibus and robust deconvolution scheme for bulk RNA sequencing data integrating multiple single-cell reference sets and prior biological knowledge.

    Chen, Chixiang / Leung, Yuk Yee / Ionita, Matei / Wang, Li-San / Li, Mingyao

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 19, Page(s) 4530–4536

    Abstract: Motivation: Cell-type deconvolution of bulk tissue RNA sequencing (RNA-seq) data is an important step toward understanding the variations in cell-type composition among disease conditions. Owing to recent advances in single-cell RNA sequencing (scRNA- ... ...

    Abstract Motivation: Cell-type deconvolution of bulk tissue RNA sequencing (RNA-seq) data is an important step toward understanding the variations in cell-type composition among disease conditions. Owing to recent advances in single-cell RNA sequencing (scRNA-seq) and the availability of large amounts of bulk RNA-seq data in disease-relevant tissues, various deconvolution methods have been developed. However, the performance of existing methods heavily relies on the quality of information provided by external data sources, such as the selection of scRNA-seq data as a reference and prior biological information.
    Results: We present the Integrated and Robust Deconvolution (InteRD) algorithm to infer cell-type proportions from target bulk RNA-seq data. Owing to the innovative use of penalized regression with a new evaluation criterion for deconvolution, InteRD has three primary advantages. First, it is able to effectively integrate deconvolution results from multiple scRNA-seq datasets. Second, InteRD calibrates estimates from reference-based deconvolution by taking into account extra biological information as priors. Third, the proposed algorithm is robust to inaccurate external information imposed in the deconvolution system. Extensive numerical evaluations and real-data applications demonstrate that InteRD yields more accurate and robust cell-type proportion estimates that agree well with known biology.
    Availability and implementation: The proposed InteRD framework is implemented in R and the package is available at https://cran.r-project.org/web/packages/InteRD/index.html.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) RNA ; Single-Cell Analysis/methods ; Gene Expression Profiling/methods ; Software ; Sequence Analysis, RNA/methods
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2022-08-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Polygenic Risk Scores in Alzheimer's Disease Genetics: Methodology, Applications, Inclusion, and Diversity.

    Clark, Kaylyn / Leung, Yuk Yee / Lee, Wan-Ping / Voight, Benjamin / Wang, Li-San

    Journal of Alzheimer's disease : JAD

    2022  Volume 89, Issue 1, Page(s) 1–12

    Abstract: The success of genome-wide association studies (GWAS) completed in the last 15 years has reinforced a key fact: polygenic architecture makes a substantial contribution to variation of susceptibility to complex disease, including Alzheimer's disease. One ... ...

    Abstract The success of genome-wide association studies (GWAS) completed in the last 15 years has reinforced a key fact: polygenic architecture makes a substantial contribution to variation of susceptibility to complex disease, including Alzheimer's disease. One straight-forward way to capture this architecture and predict which individuals in a population are most at risk is to calculate a polygenic risk score (PRS). This score aggregates the risk conferred across multiple genetic variants, ultimately representing an individual's predicted genetic susceptibility for a disease. PRS have received increasing attention after having been successfully used in complex traits. This has brought with it renewed attention on new methods which improve the accuracy of risk prediction. While these applications are initially informative, their utility is far from equitable: the majority of PRS models use samples heavily if not entirely of individuals of European descent. This basic approach opens concerns of health equity if applied inaccurately to other population groups, or health disparity if we fail to use them at all. In this review we will examine the methods of calculating PRS and some of their previous uses in disease prediction. We also advocate for, with supporting scientific evidence, inclusion of data from diverse populations in these existing and future studies of population risk via PRS.
    MeSH term(s) Alzheimer Disease/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Humans ; Multifactorial Inheritance/genetics ; Risk Factors
    Language English
    Publishing date 2022-06-30
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-220025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Tailor: Targeting heavy tails in flow cytometry data with fast, interpretable mixture modeling.

    Ionita, Matei / Schretzenmair, Richard / Jones, Derek / Moore, Jonni / Wang, Li-San / Rogers, Wade

    Cytometry. Part A : the journal of the International Society for Analytical Cytology

    2021  Volume 99, Issue 2, Page(s) 133–144

    Abstract: Automated clustering workflows are increasingly used for the analysis of high parameter flow cytometry data. This trend calls for algorithms which are able to quickly process tens of millions of data points, to compare results across subjects or time ... ...

    Abstract Automated clustering workflows are increasingly used for the analysis of high parameter flow cytometry data. This trend calls for algorithms which are able to quickly process tens of millions of data points, to compare results across subjects or time points, and to provide easily actionable interpretations of the results. To this end, we created Tailor, a model-based clustering algorithm specialized for flow cytometry data. Our approach leverages a phenotype-aware binning scheme to provide a coarse model of the data, which is then refined using a multivariate Gaussian mixture model. We benchmark Tailor using a simulation study and two flow cytometry data sets, and show that the results are robust to moderate departures from normality and inter-sample variation. Moreover, Tailor provides automated, non-overlapping annotations of its clusters, which facilitates interpretation of results and downstream analysis. Tailor is released as an R package, and the source code is publicly available at www.github.com/matei-ionita/Tailor.
    MeSH term(s) Algorithms ; Cluster Analysis ; Flow Cytometry ; Humans ; Normal Distribution ; Software
    Language English
    Publishing date 2021-01-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2099868-5
    ISSN 1552-4930 ; 0196-4763 ; 1552-4922
    ISSN (online) 1552-4930
    ISSN 0196-4763 ; 1552-4922
    DOI 10.1002/cyto.a.24307
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Region-based analysis with functional annotation identifies genes associated with cognitive function in South Asians from India.

    Abu-Amara, Hasan / Zhao, Wei / Li, Zheng / Leung, Yuk Yee / Schellenberg, Gerard D / Wang, Li-San / Moorjani, Priya / Dey, A B / Dey, Sharmitha / Zhou, Xiang / Gross, Alden L / Lee, Jinkook / Kardia, Sharon L R / Smith, Jennifer A

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been ... ...

    Abstract The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been identified from studies conducted in European Ancestry (EA) but are unknown in South Asians. Using whole-genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD), we performed a gene-based analysis of 84 genes previously associated with AD in EA. We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. For each gene, we examined missense/loss-of-function (LoF) variants and brain-specific promoter/enhancer variants, separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores) using the variant-Set Test for Association using Annotation infoRmation (STAAR). In the missense/LoF analysis without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes had an association with at least one measure of cognitive function (FDR q<0.1).
    Language English
    Publishing date 2024-01-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.18.24301482
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: HiPR: High-throughput probabilistic RNA structure inference.

    Kuksa, Pavel P / Li, Fan / Kannan, Sampath / Gregory, Brian D / Leung, Yuk Yee / Wang, Li-San

    Computational and structural biotechnology journal

    2020  Volume 18, Page(s) 1539–1547

    Abstract: Recent high-throughput structure-sensitive genome-wide sequencing-based assays have enabled large-scale studies of RNA structure, and robust transcriptome-wide computational prediction of individual RNA structures across RNA classes from these assays has ...

    Abstract Recent high-throughput structure-sensitive genome-wide sequencing-based assays have enabled large-scale studies of RNA structure, and robust transcriptome-wide computational prediction of individual RNA structures across RNA classes from these assays has potential to further improve the prediction accuracy. Here, we describe HiPR, a novel method for RNA structure prediction at single-nucleotide resolution that combines high-throughput structure probing data (DMS-seq, DMS-MaPseq) with a novel probabilistic folding algorithm. On validation data spanning a variety of RNA classes, HiPR often increases accuracy for predicting RNA structures, giving researchers new tools to study RNA structure.
    Language English
    Publishing date 2020-06-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2020.06.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: The prediction of Alzheimer's disease through multi-trait genetic modeling.

    Clark, Kaylyn / Fu, Wei / Liu, Chia-Lun / Ho, Pei-Chuan / Wang, Hui / Lee, Wan-Ping / Chou, Shin-Yi / Wang, Li-San / Tzeng, Jung-Ying

    Frontiers in aging neuroscience

    2023  Volume 15, Page(s) 1168638

    Abstract: To better capture the polygenic architecture of Alzheimer's disease (AD), we developed a joint genetic score, MetaGRS. We incorporated genetic variants for AD and 24 other traits from two independent cohorts, NACC ( ...

    Abstract To better capture the polygenic architecture of Alzheimer's disease (AD), we developed a joint genetic score, MetaGRS. We incorporated genetic variants for AD and 24 other traits from two independent cohorts, NACC (
    Language English
    Publishing date 2023-07-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2023.1168638
    Database MEDical Literature Analysis and Retrieval System OnLINE

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