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Heejung Shim

Publications and source records attributed to Heejung Shim.

3 recordsLinked to original sources
PubMed2025

simPIC:flexible simulation of paired-insertion counts for single-cell ATAC sequencing data.

Single-cell Assay for Transposase Accessible Chromatin (scATAC-seq) is increasingly used at population scale to study how genetic variation shapes chromatin accessibility across diverse cell types. This widespread adoption of the assay has created a need for computational methods that can handle complex biological and technical variation. Yet method development is limited by the lack of flexible simulation tools with known ground truth. Here, we present simPIC, a simulation framework for generating realistic single-cell ATAC-seq data across individuals and cell types. simPIC supports both population-scale and single-individual simulations, with the ability to model cell groups, batch effects, and genotype-dependent variation in accessibility. These features enable realistic benchmarking for tasks such as chromatin accessibility quantitative trait locus (caQTL) mapping. simPIC generates data that closely match real datasets and better captures inter-individual and experimental variation compared to existing tools.

simulation↗
PubMed2025

A hierarchical, count-based model highlights challenges in scATAC-seq data analysis and points to opportunities to extract finer-resolution information.

BACKGROUND: Data from Single-cell Assay for Transposase Accessible Chromatin with Sequencing (scATAC-seq) is highly sparse. While current computational methods feature a range of transformation procedures to extract meaningful information, major challenges remain. RESULTS: Here, we discuss the major scATAC-seq data analysis challenges such as sequencing depth normalization and region-specific biases. We present a hierarchical count model that is motivated by the data generating process of scATAC-seq data. Our simulations show that current scATAC-seq data, while clearly containing physical single-cell resolution, are too sparse to infer true informational-level single-cell, single-region of chromatin accessibility states. CONCLUSIONS: While the broad utility of scATAC-seq at a cell type level is undeniable, describing it as fully resolving chromatin accessibility at single-cell resolution, particularly at individual locus level, may overstate the level of detail currently achievable. We conclude that chromatin accessibility profiling at true single-cell, single-region resolution is challenging with current data sensitivity, but that it may be achieved with promising developments in optimizing the efficiency of scATAC-seq assays.

Single-Cell Analysis↗
PubMed2025

A paradoxical population structure of var DBLα types in Africa.

The var multigene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of var genes by specific upstream sequences (upsA, B, or C). Var with these ups groups have different chromosomal locations, transcriptional directions, and associations with disease severity. Here we explore temporal and spatial diversity of a region of var genes encoding the DBLα domain of PfEMP1 in Africa. By applying a novel ups classification algorithm (cUps) to publicly-available DBLα sequence datasets, we categorised DBLα according to association with the three ups groups, thereby avoiding the need to sequence complete genes. Data from deep sequencing of DBLα types in a local population in northern Ghana surveyed seven times from 2012 to 2017 found variants with rare-to-moderate-to-extreme frequencies, and the common variants were temporally stable in this local endemic area. Furthermore, we observed that every isolate repertoire, whether mono- or multiclonal, comprised DBLα types occurring with these frequency ranges implying a common genome structure. When comparing African countries of Ghana, Gabon, Malawi, and Uganda, we report that some DBLα types were consistently found at high frequencies in multiple African countries while others were common only at the country level. The implication of these local and pan-Africa population patterns is discussed in terms of advantage to the parasite with regards to within-host adaptation and resilience to malaria control.

Plasmodium falciparum↗