Biology subjects

Pingili, M.

Publications and source records attributed to Pingili, M..

3 recordsLinked to original sources

bioRxiv2026

Characterizing cellular subpopulations critical to treatment response in autoimmune diseases

Single-cell RNA sequencing provides a powerful approach for characterizing cell types, states, and lineages within heterogeneous tissues. However, identifying cell subpopulations that drive phenotypes, particularly treatment responses, remains a challenge. In this study, we performed comprehensive analyses to identify treatment response-associated cell subpopulations in autoimmune diseases by mapping bulk response information onto single-cell data. We integrated single-cell and bulk biopsy data from 314 responders and 619 non-responders treated with six therapeutics targeting tumor necrosis factor (TNF), integrin, or interleukin pathways in inflammatory bowel diseases (IBD) and psoriasis (PsO). Our analyses captured 128,428 interactions among 3,617 differentially expressed genes (DEGs), 852 pathways, and nine cell types spanning immune, stromal, and epithelial compartments. The importance of epithelial barrier integrity and enterocyte-mediated permeability in responses and inflammatory signaling in macrophages in non-responses in all tested therapies were highlighted by the presence of shared DEGs and pathways in both Crohns disease (CD) and ulcerative colitis (UC). In PsO, keratinocytes drove non-response to integrin-targeting therapies via disrupted adhesion, migration, and sustained epidermal inflammation. Additionally we introduce SCTRAD (https://immbioinfoabbv.shinyapps.io/SCTRAD/), an online web-based platform that allows exploration of mechanisms that influence the heterogeneity of cellular responses through DEGs and pathways at the single-cell level, as well as analysis of the cell-type-specific drug-related gene network. Our findings provide a comprehensive analysis of the role of cellular heterogeneity in treatment outcomes and for advancing precision medicine strategies in autoimmune diseases.

immunology↗

bioRxiv2025

scCompare: a web app for single-cell RNA sequencing dataset comparisons across multiple auto-immune diseases

MotivationSingle-cell RNA sequencing (scRNA-seq) datasets have been widely used to identify the cell types and marker genes with pivotal roles in driving pathogenesis and progression of auto-immune diseases. Comparative analysis of different cell types or diseases across multiple scRNA-seq datasets can reveal the homogeneous and heterogeneous pathogenesis, and a comprehensive web-based comparison tool that could streamline this process is not yet available. ResultsWe introduce scCompare, a web-based platform for scRNA-seq comparisons in autoimmune diseases. scCompare includes 2,125 differential gene lists from 100 scRNA-seq datasets in 22 auto-immune diseases and a query system supporting 170 standardized keywords from four attributes (disease, cell type, tissue, and treatment). scCompare also provides three modules enabling several comparative analysis and visualization options. geneQuery supports comparisons of queried genes across differential gene lists identified from multiple scRNA-seq datasets. DEGEnricher performs cell-type-specific enrichment analysis across studies based on a user-input gene list. DEGCompare allows interactive comparisons of multiple differential gene lists of many studies and performs pathway enrichment analyses. Using two case studies as examples, we demonstrated that scCompare represents a unique platform for biologists to identify, compare and validate the pathogenesis at the single-cell levels among auto-immune diseases. Availability and implementationscCompare is freely available at https://sccompare.shinyapps.io/main/. The source code is available at https://github.com/abbviegrc/scCompare.

bioinformatics↗

bioRxiv2025

Estimating the effect of tissue- and blood-derived cell reference matrices on deconvolving bulk transcriptomic datasets

BackgroundCell deconvolution is a method used to characterize the composition of the mixed cell population in bulk transcriptomic datasets. Tissue- and blood-derived cell reference matrices (CRMs) are typically used, but their impact on deconvolution has yet to be evaluated. MethodsRecursive feature elimination and random forest methods were applied to build tissue- and blood-derived CRMs using single-cell RNA sequencing (scRNA-seq) datasets of inflammatory bowel disease (IBD) which comprises two subtypes (Crohns disease (CD) and ulcerative colitis (UC)). Combining with three published blood-derived CRMs (IRIS, LM22, and ImmunoStates), public bulk transcriptomes datasets and simulated datasets generated from scRNA-Seq were used to evaluate the deconvolution performance by goodness-of-fit and cell fractions correlation. Additionally, two infliximab-treated bulk datasets were used to compare the treatment-related cell types revealed by tissue- and blood-derived CRMs. Lung adenocarcinoma (LUAD) single-cell and TCGA bulk transcriptomic datasets were also used for evaluation. ResultsFor CD and UC tissue bulk datasets, tissue-derived CRMs showed better deconvolution goodness-of-fit scores compared to blood-derived CRMs. Meanwhile, tissue-derived CRMs represented more accurate cellular proportion estimates for most cell types, such as immune and stromal cells in tissue pseudobulk datasets. They also revealed more treatment-related cell types. Additionally, CRMs derived from the scRNA-seq datasets from CD and UC colon samples had similar performance. In contrast, CRMs derived from CD ileum scRNA-seq dataset had better performance in the ileum bulk datasets. All CRMs yielded consistent deconvolution performance when deconvolving blood bulk transcriptomics. The similar results have also been shown using LUAD datasets. ConclusionsOur results emphasize the importance of selecting appropriate CRMs for cell deconvolution, particularly in bulk tissue transcriptomes in immunology and oncology. Such considerations can be extended to encompass other disease implications. AbbVie Disclosure statementAll authors are current employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. Key PointsO_LITissue-derived CRMs showed higher goodness-of-fit compared to blood-derived CRMs for deconvolving bulk tissue transcriptomics. C_LIO_LIAll CRMs yield consistent goodness-of-fit for deconvolving bulk blood transcriptomics. C_LIO_LITissue-derived CRMs represent more accurate cellular proportion estimates and reveal more treatment-related cell types, and the specific tissue type is relevant to the deconvolution performance. C_LI

bioinformatics↗