Advances and challenges in cell–cell communication inference: a comprehensive review of tools, resources, and future directions

Briefings in Bioinformatics, vol. 26

Abstract

Recent advancements in high-resolution and high-throughput sequencing technologies have significantly enhanced the study of cell-cell communication inference using single-cell and spatial transcriptomics data. Over the past 6 years, this growing interest has led to the development of more than 100 bioinformatics tools and nearly 50 resources, primarily in the form of ligand-receptor databases. These tools vary widely in their requirements, scoring approaches, ability to infer inter- and/or intra-cellular communication, assumptions, and limitations. Similarly, cell-cell communication resources differ in many aspects, mainly in the number of annotated interactions, species coverage, and their focus on inter-cellular signaling or both inter- and intra-cellular communication. This abundance and diversity create challenges in identifying compatible and suitable tools and resources to meet specific user needs. In this collaborative effort, we aim to provide a comprehensive report on the current state of cell-cell communication analysis derived from single-cell or spatial transcriptomics data. The report reviews existing methods and resources, addressing all relevant aspects from the user's perspective. It also explores current limitations, pitfalls, and unresolved issues in cell-cell communication inference, offering an aggregated analysis of the existing literature on the topic. Furthermore, we highlight potential future directions in the field and consolidate the collected knowledge into CCC-Catalog (https://sysbiobig.gitlab.io/ccc-catalog), a centralized web platform designed to serve as a hub for bioinformaticians and researchers interested in cell-cell communication inference.

Authors 12

1. Giulia Cesaro

   University of Padua

   Affiliation as printed

   Department of Information Engineering, University of Padova , Via Gradenigo 6/B, 35131, Padova ,

2. James Shiniti Nagai Aachen Institute for Computational Genomics

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen Medical Faculty, Institute for Computational Genomics , Pauwelsstrasse 19, 52074, Aachen ,

3. Nicolò Gnoato

   University of Padua

   Affiliation as printed

   Department of Biology, University of Padova , Via Ugo Bassi 58/B, 35131, Padova ,

4. Alice Chiodi

   Institute of Biomedical Technologies

   Affiliation as printed

   Institute of Biomedical Technologies, National Research Council (CNR) , Via F.lli Cervi 93, 20054, Segrate (Milan) ,

5. Gaia Tussardi

   University of Padua

   Affiliation as printed

   Department of Information Engineering, University of Padova , Via Gradenigo 6/B, 35131, Padova ,

6. Vanessa Klöker Aachen Institute for Computational Genomics

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen Medical Faculty, Institute for Computational Genomics , Pauwelsstrasse 19, 52074, Aachen ,

7. Carmelo Vittorio Musumarra

   University of Padua

   Affiliation as printed

   Department of Biology, University of Padova , Via Ugo Bassi 58/B, 35131, Padova ,

8. Ettore Mosca

   Institute of Biomedical Technologies

   Affiliation as printed

   Institute of Biomedical Technologies, National Research Council (CNR) , Via F.lli Cervi 93, 20054, Segrate (Milan) ,

9. Ivan G. Costa Aachen Institute for Computational Genomics

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen Medical Faculty, Institute for Computational Genomics , Pauwelsstrasse 19, 52074, Aachen ,

10. Barbara Di Camillo

    University of Padua

    Affiliation as printed

    Department of Information Engineering, University of Padova , Via Ugo Bassi 58/B, 35131, Padova ,

11. Enrica Calura

    University of Padua

    Affiliation as printed

    Department of Biology, University of Padova , Via Ugo Bassi 58/B, 35131, Padova ,

12. Giacomo Baruzzo corresponding

    University of Padua

    Affiliation as printed

    Department of Information Engineering, University of Padova , Via Gradenigo 6/B, 35131, Padova ,