New Scientific Publications from the DOCTIS Project

 

 

The DOCTIS project has recently published several scientific publications that shed light on crucial advancements in single-cell genomics and potential therapeutic strategies for preventing severe COVID-19.

One of the publications, titled “Sampling Time-Dependent Artifacts in Single-Cell Genomic Studies,” highlights the challenges posed by technical biases during sample acquisition in large-scale single-cell RNA and ATAC sequencing experiments. The researchers report the identification of gene expression and chromatin accessibility artifacts introduced during sampling and propose experimental and computational solutions to prevent these issues. This study emphasizes the importance of benchmarking and ensuring the reproducibility of results in single-cell genomics research.

DocTIS Scientific publication graphic
The impact of sampling time on single-cell transcriptional and open chromatin profiles

In another publication entitled “FixNCut: Single-Cell Genomics through Reversible Tissue Fixation and Dissociation,” the partners of DOCTIS project introduces a novel methodology for preserving tissue samples and overcoming limitations in single-cell genomics. The FixNCut technique involves the reversible fixation of tissue followed by dissociation, resulting in preserved RNA integrity, sequencing library complexity, and cellular composition. The researchers demonstrate the effectiveness of FixNCut in human and mouse tissues, offering a versatile tool for robust and flexible study designs across various single-cell and spatial technologies.

DocTIS Scientific publication graphic
FixNCut protocol in human peripheral blood mononuclear cells (PBMCs).

The third publication, titled “Targeting the CD80/86 Proinflammatory Axis as a Therapeutic Strategy to Prevent Severe COVID-19,” focuses on the excessive immune response known as cytokine storm observed in severe COVID-19 cases. Based on epidemiological evidence, the researchers hypothesized that blocking the CD80/86 signaling pathway could be an effective therapeutic approach to mitigate the hyperinflammation seen in severe COVID-19. Through exploratory evidence and analysis of blood samples from rheumatic patients treated with abatacept, a drug that blocks CD80/86 co-stimulation, the study reveals promising results in antagonizing the proinflammatory processes elicited by COVID-19. These findings support abatacept as a potential candidate for preventing severe COVID-19.

DocTIS Scientific publication graphic
Expression of the cell-type specific markers defining the cell clusters representing the three elements of the CD80/86 axis.

Lastly, the DOCTIS project partners present a dynamic single-cell-based framework for creating digital twins in a publication titled “A Dynamic Single Cell-Based Framework for Digital Twins to Prioritize Disease Genes and Drug Targets”. The framework addresses the challenges of organizing and prioritizing disease-associated changes in digital twins for drug discovery and treatment. The researchers developed a scalable framework using time-series single-cell RNA-sequencing data to construct multicellular network models. These models allow the identification of upstream regulators for biomarker discovery and drug development. The framework was successfully applied to seasonal allergic rhinitis and other inflammatory diseases, enabling the prioritization of upstream regulators.

DocTIS Scientific publication graphic
Construction of MNMs and prioritization of URs

The scientific publications from the DOCTIS project provide valuable insights into the advancement of single-cell genomics and the development of potential therapeutic strategies. Researchers, clinicians, and biotech companies can access the detailed findings and methodologies by visiting https://doctis.eu/results/. These discoveries hold significant promise for revolutionizing biomedical research and improving patient outcomes in the future.

The DoCTIS project has received funding from the European Union’s H2020 reearch and innovation program under grant agreement 848028.