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  1. Free, publicly-accessible full text available December 5, 2023
  2. Abstract Motivation

    Identification of human genes involved in the aging process is critical due to the incidence of many diseases with age. A state-of-the-art approach for this purpose infers a weighted dynamic aging-specific subnetwork by mapping gene expression (GE) levels at different ages onto the protein–protein interaction network (PPIN). Then, it analyzes this subnetwork in a supervised manner by training a predictive model to learn how network topologies of known aging- versus non-aging-related genes change across ages. Finally, it uses the trained model to predict novel aging-related gene candidates. However, the best current subnetwork resulting from this approach still yields suboptimal prediction accuracy. This could be because it was inferred using outdated GE and PPIN data. Here, we evaluate whether analyzing a weighted dynamic aging-specific subnetwork inferred from newer GE and PPIN data improves prediction accuracy upon analyzing the best current subnetwork inferred from outdated data.

    Results

    Unexpectedly, we find that not to be the case. To understand this, we perform aging-related pathway and Gene Ontology term enrichment analyses. We find that the suboptimal prediction accuracy, regardless of which GE or PPIN data is used, may be caused by the current knowledge about which genes are aging-related being incomplete, or by themore »current methods for inferring or analyzing an aging-specific subnetwork being unable to capture all of the aging-related knowledge. These findings can potentially guide future directions towards improving supervised prediction of aging-related genes via -omics data integration.

    Availability and implementation

    All data and code are available at zenodo, DOI: 10.5281/zenodo.6995045.

    Supplementary information

    Supplementary data are available at Bioinformatics Advances online.

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  3. Free, publicly-accessible full text available October 3, 2023
  4. Free, publicly-accessible full text available August 14, 2023
  5. Free, publicly-accessible full text available August 14, 2023
  6. Free, publicly-accessible full text available July 8, 2023
  7. Abstract

    Genome-wide profiling of chromatin accessibility by DNase-seq or ATAC-seq has been widely used to identify regulatory DNA elements and transcription factor binding sites. However, enzymatic DNA cleavage exhibits intrinsic sequence biases that confound chromatin accessibility profiling data analysis. Existing computational tools are limited in their ability to account for such intrinsic biases and not designed for analyzing single-cell data. Here, we present Simplex Encoded Linear Model for Accessible Chromatin (SELMA), a computational method for systematic estimation of intrinsic cleavage biases from genomic chromatin accessibility profiling data. We demonstrate that SELMA yields accurate and robust bias estimation from both bulk and single-cell DNase-seq and ATAC-seq data. SELMA can utilize internal mitochondrial DNA data to improve bias estimation. We show that transcription factor binding inference from DNase footprints can be improved by incorporating estimated biases using SELMA. Furthermore, we show strong effects of intrinsic biases in single-cell ATAC-seq data, and develop the first single-cell ATAC-seq intrinsic bias correction model to improve cell clustering. SELMA can enhance the performance of existing bioinformatics tools and improve the analysis of both bulk and single-cell chromatin accessibility sequencing data.

  8. Free, publicly-accessible full text available April 28, 2023
  9. Free, publicly-accessible full text available June 1, 2023