Extended Data Fig. 7: LIANA+ generates interpretable and reliable predictions from complex datasets.
From: LIANA+ provides an all-in-one framework for cell–cell communication inference
A) Applying LIANA+ on Myocardial infarction substantially reduced the prediction space to yield an interpretable subset of predictions. (1) inference of the full possible prediction space of ligand-receptor interactions across 110 cell-type pairs, 28 samples, and 3 conditions. (2) Incorporation of spatially associated cell-type pairs (III). (3) Inclusion of information about spatially-colocalised ligand-receptor interactions (LRs), identified using (I) local scores with non-negative matrix factorization (II). (4) Multi-view factor analysis using LRs predicted from single-cell data and informed by the spatial analysis. (5) Targeted differential expression analysis to find significantly deregulated LRs in a specific pair of interacting literature-supported cell types (‡). (6) A causal network search to generate a specific mechanistic hypothesis linking LR interactions to downstream Transcription Factors (TFs). The TF activities were estimated using a curated TF-target network80 (IV) and linked to the LRs using a protein–protein interaction network22. B) Mean silhouette scores of clustering heart failure versus healthy myeloid samples using genes extracted from CCC predictions across the distinct steps shown in subpanel A. Silhouette scores were z-transformed using randomly permuted gene sets of the same size as a baseline. The red dashed line signifies a z-score of 1.645, equivalent to a significant one-sided z-test. C) Adjusted Rand Index (ARI) across the distinct steps shown in subpanel A. The central line within each box marks the median, with the box hinges representing the first and third quartiles. The whiskers extend up to 1.5 times the interquartile range above and below the box hinges. Hollow points represent outliers. In the evaluation, Steps 1 and I were respectively represented by prediction averages from CellPhoneDB P-values and SpatialDM’s Global Moran’s R across samples (Methods). D) Histogram of ARI values for Step 6, with one-sided empirical P-values calculated against a random distribution generated using sets of genes of the same size as the predictions in each step. The grey boxes depict the frequency of values drawn at random; the blue dashed line corresponds to the actual value. Source numerical data are available in source data.
