Systems Biology of Single Cells: Bridging Genomics and Functional Insights

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Bioinformatics".

Deadline for manuscript submissions: 15 June 2026 | Viewed by 1543

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Laboratory of Applied Biotechnology, Sāo Paulo State University (UNESP), Botucatu, SP, Brazil
Interests: bioinformatics; cytogenomics; systems biology; evolutionary biology; celular stressors
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Special Issue Information

Dear Colleagues,

Systems biology is a fruitful field focused on studying biological systems from a holistic rather than a reductionist perspective. This means that this area allows researchers to find, study, and describe the emergent properties of biological systems, which is not possible under reductionist views. This field provides unprecedented knowledge in many areas, including molecular and cell biology. In these cases, we have observed that the molecular mechanisms driving biological processes are much more intricate than previously thought. Single-cell RNA-Seq (scRNA-Seq) is a field in which scientists can analyze gene expression at the single-cell level. Overall, this approach is showing us that the complexity of expression in tissues is much more diverse and complex than previously thought. ScRNA-Seq evolved to study the cell-gene expression in situ, that is, in tissue samples, a technique called spatial transcriptomics. More recently, systems biology, scRNA-Seq, and spatial transcriptomics have been merged, allowing for astonishing discoveries concerning how each cell system behaves. Given the complexity of analyzing biological systems, new tools, approaches, concepts, and strategies focusing on systems biology, particularly in the context of single-cell RNA sequencing (scRNA-Seq) and spatial transcriptomes, have been emerging. Therefore, the authors are encouraged to submit original manuscripts concerning systems biology studies in scRNA-Seq and spatial transcriptomics. In this case, manuscripts describing new methods, approaches, ideas, or utilizing systems biology and graph theory to analyze these data in any field are welcome. Reviews and data reanalysis focusing on these themes will also be considered. Note that robust bioinformatics research should integrate both computational analyses and experimental biological validation.

Dr. Guilherme Targino Valente
Guest Editor

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Keywords

  • systems biology
  • graph theory
  • single-cell RNA-Seq
  • spatial transcriptomics
  • molecular networks
  • complex networks

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Published Papers (1 paper)

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Research

21 pages, 11218 KB  
Article
Multi-Modal Profiling Reveals SERPINB3-Driven Immune Evasion and Stromal Immune Mimicry in Triple-Negative Breast Cancer
by Zinab O. Doha
Genes 2026, 17(1), 38; https://doi.org/10.3390/genes17010038 - 31 Dec 2025
Viewed by 856
Abstract
Background/Objectives: Triple-negative breast cancer (TNBC) exhibits high immune infiltration yet remains clinically aggressive. Although immune checkpoint blockade benefits a subset of patients, the molecular programs enabling concurrent immune activation and immune evasion in TNBC are not fully defined. This study aimed to identify [...] Read more.
Background/Objectives: Triple-negative breast cancer (TNBC) exhibits high immune infiltration yet remains clinically aggressive. Although immune checkpoint blockade benefits a subset of patients, the molecular programs enabling concurrent immune activation and immune evasion in TNBC are not fully defined. This study aimed to identify TNBC-specific tumor-intrinsic and tumor-extrinsic molecular features that may explain this paradox. Methods: Publicly available single-cell RNA-sequencing data from primary breast tumors were analyzed to characterize subtype-specific transcriptional programs across epithelial and stromal compartments. Tumor-intrinsic findings were independently validated using bulk transcriptomic and clinical data from the METABRIC cohort. Tumor microenvironment remodeling was evaluated using multiplexed tissue imaging of TNBC tumors. Functional analyses were done included Gene Ontology enrichment, Hallmark gene set enrichment analysis, and SERPINB3-centered protein–protein interaction network analysis using STRING. Results: Single-cell analysis identified SERPINB3 as a TNBC-enriched epithelial gene relative to ER+ and HER2+ tumors. This subtype-restricted pattern was validated in the METABRIC cohort and associated with pathways related to epithelial–mesenchymal transition, interferon signaling, and antigen presentation. TNBC tumors also displayed a humoral immune signature characterized by B-cell and plasmablast enrichment, as well as ectopic immunoglobulin gene expression in cancer-associated fibroblasts, endothelial cells, and myeloid populations. Multiplex imaging revealed coordinated associations between immune suppression, stromal activation, and tumor proliferation. Network analysis placed SERPINB3 within interconnected immune-regulatory and stromal signaling modules. Conclusions: Together, these data indicate that TNBC exhibits co-existing immune activation and immune-suppressive features. The identified epithelial and stromal signatures represent candidate biomarkers that may inform future studies of immune regulation and therapeutic stratification in TNBC. Full article
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