Matching single cells across modalities with contrastive learning and optimal transport.

Understanding the interactions between the biomolecules that govern cellular behaviors remains an emergent question in biology. Recent advances in single-cell technologies have enabled the simultaneous quantification of multiple biomolecules in the same cell, opening new avenues for understanding cellular complexity and heterogeneity. Still, the resulting multimodal single-cell datasets present unique challenges arising from the high dimensionality and multiple sources of acquisition noise. Computational methods able to match cells across different modalities offer an appealing alternative towards this goal. In this work, we propose MatchCLOT, a novel method for modality matching inspired by recent promising developments in contrastive learning and optimal transport. MatchCLOT uses contrastive learning to learn a common representation between two modalities and applies entropic optimal transport as an approximate maximum weight bipartite matching algorithm. Our model obtains state-of-the-art performance on two curated benchmarking datasets and an independent test dataset, improving the top scoring method by 26.1% while preserving the underlying biological structure of the multimodal data. Importantly, MatchCLOT offers high gains in computational time and memory that, in contrast to existing methods, allows it to scale well with the number of cells. As single-cell datasets become increasingly large, MatchCLOT offers an accurate and efficient solution to the problem of modality matching.

scQUEST: Quantifying tumor ecosystem heterogeneity from mass or flow cytometry data.

With mass and flow cytometry, millions of single-cell profiles with dozens of parameters can be measured to comprehensively characterize complex tumor ecosystems. Here, we present scQUEST, an open-source Python library for cell type identification and quantification of tumor ecosystem heterogeneity in patient cohorts. We provide a step-by-step protocol on the application of scQUEST on our previously generated human breast cancer single-cell atlas using mass cytometry and discuss how it can be adapted and extended for other datasets and analyses. For complete details on the use and execution of this protocol, please refer to Wagner et al. (2019).

ATHENA: analysis of tumor heterogeneity from spatial omics measurements.

SUMMARY: Tumor heterogeneity has emerged as a fundamental property of most human cancers, with broad implications for diagnosis and treatment. Recently, spatial omics have enabled spatial tumor profiling, however computational resources that exploit the measurements to quantify tumor heterogeneity in a spatially aware manner are largely missing. We present ATHENA (Analysis of Tumor HEterogeNeity from spAtial omics measurements), a computational framework that facilitates the visualization, processing and analysis of tumor heterogeneity from spatial omics measurements. ATHENA uses graph representations of tumors and bundles together a large collection of established and novel heterogeneity scores that quantify different aspects of the complexity of tumor ecosystems. AVAILABILITY AND IMPLEMENTATION: ATHENA is available as a Python package under an open-source license at: https://github.com/AI4SCR/ATHENA. Detailed documentation and step-by-step tutorials with example datasets are also available at: https://ai4scr.github.io/ATHENA/. The data presented in this article are publicly available on Figshare at https://figshare.com/articles/dataset/zurich_pkl/19617642/2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Quantification of tumor heterogeneity: from data acquisition to metric generation.

Tumors are unique and complex ecosystems, in which heterogeneous cell subpopulations with variable molecular profiles, aggressiveness, and proliferation potential coexist and interact. Understanding how heterogeneity influences tumor progression has important clinical implications for improving diagnosis, prognosis, and treatment response prediction. Several recent innovations in data acquisition methods and computational metrics have enabled the quantification of spatiotemporal heterogeneity across different scales of tumor organization. Here, we summarize the most promising efforts from a common experimental and computational perspective, discussing their advantages, shortcomings, and challenges. With personalized medicine entering a new era of unprecedented opportunities, our vision is that of future workflows integrating across modalities, scales, and dimensions to capture intricate aspects of the tumor ecosystem and to open new avenues for improved patient care.