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Kevin Z. Lin

Publications and source records attributed to Kevin Z. Lin.

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All the single cells: single-cell transcriptomics/epigenomics experimental design and analysis considerations for glial biologists

Single-cell transcriptomics, epigenomics, and other 'omics applied at single-cell resolution can significantly advance hypotheses and understanding of glial biology. Omics technologies are revealing a large and growing number of new glial cell subtypes, defined by their gene expression profile. These subtypes have significant implications for understanding glial cell function, cell-cell communications, and glia-specific changes between homeostasis and conditions such as neurological disease. For many, the training in how to analyze, interpret, and understand these large datasets has been through reading and understanding literature from other fields like biostatistics. Here, we provide a primer for glial biologists on experimental design and analysis of single-cell RNA-seq datasets. Our goal is to further the understanding of why decisions might be made about datasets and to enhance biologists' ability to interpret and critique their work and the work of others. We review the steps involved in single-cell analysis with a focus on decision points and particular notes for glia. The goal of this primer is to ensure that single-cell 'omics experiments continue to advance glial biology in a rigorous and replicable way.

q-bio.QM

Controlled Analyses of Social Biases in Wikipedia Bios

Social biases on Wikipedia, a widely-read global platform, could greatly influence public opinion. While prior research has examined man/woman gender bias in biography articles, possible influences of other demographic attributes limit conclusions. In this work, we present a methodology for analyzing Wikipedia pages about people that isolates dimensions of interest (e.g., gender), from other attributes (e.g., occupation). Given a target corpus for analysis (e.g.~biographies about women), we present a method for constructing a comparison corpus that matches the target corpus in as many attributes as possible, except the target one. We develop evaluation metrics to measure how well the comparison corpus aligns with the target corpus and then examine how articles about gender and racial minorities (cis. women, non-binary people, transgender women, and transgender men; African American, Asian American, and Hispanic/Latinx American people) differ from other articles. In addition to identifying suspect social biases, our results show that failing to control for covariates can result in different conclusions and veil biases. Our contributions include methodology that facilitates further analyses of bias in Wikipedia articles, findings that can aid Wikipedia editors in reducing biases, and a framework and evaluation metrics to guide future work in this area.

cs.CL

Bias-adjusted spectral clustering in multi-layer stochastic block models

We consider the problem of estimating common community structures in multi-layer stochastic block models, where each single layer may not have sufficient signal strength to recover the full community structure. In order to efficiently aggregate signal across different layers, we argue that the sum-of-squared adjacency matrices contain sufficient signal even when individual layers are very sparse. Our method uses a bias-removal step that is necessary when the squared noise matrices may overwhelm the signal in the very sparse regime. The analysis of our method relies on several novel tail probability bounds for matrix linear combinations with matrix-valued coefficients and matrix-valued quadratic forms, which may be of independent interest. The performance of our method and the necessity of bias removal is demonstrated in synthetic data and in microarray analysis about gene co-expression networks.

math.ST

Covariance-based sample selection for heterogeneous data: Applications to gene expression and autism risk gene detection

Risk for autism can be influenced by genetic mutations in hundreds of genes. Based on findings showing that genes with highly correlated gene expressions are functionally interrelated, "guilt by association" methods such as DAWN have been developed to identify these autism risk genes. Previous research analyzes the BrainSpan dataset, which contains gene expression of brain tissues from varying regions and developmental periods. Since the spatiotemporal properties of brain tissue is known to affect the gene expression's covariance, previous research have focused only on a specific subset of samples to avoid the issue of heterogeneity. This leads to a potential loss of power when detecting risk genes. In this article, we develop a new method called COBS (COvariance-Based sample Selection) to find a larger and more homogeneous subset of samples that share the same population covariance matrix for the downstream DAWN analysis. To demonstrate COBS's effectiveness, we utilize genetic risk scores from two sequential data freezes obtained in 2014 and 2019. We show COBS improves DAWN's ability to predict risk genes detected in the newer data freeze when utilizing the risk scores of the older data freeze as input.

stat.ME