Multimodal single-cell assays provide high-resolution snapshots of complex cell populations, but are mostly limited to transcriptome plus an additional modality. Here, we describe expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq) for the high-throughput characterization of at least five modalities of information from each single cell. We demonstrate application of ECCITE-seq to multimodal CRISPR screens with robust direct single-guide RNA capture and to clonotype-aware multimodal phenotyping of cancer samples. ECCITE-seq combines the single-cell analysis of multiple modalities, for example transcriptome, immune cell receptors, cell surface proteins and single-guide RNAs.

Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells