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Updated: May 17, 2026

An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects

An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects

Published on: January 9, 2020

MOSAIC: A Spectral Framework for Integrative Phenotypic Characterization Using Population-Level Single-Cell

Chang Lu^1,2, Yuval Kluger^1,2,3, Rong Ma^4,5,6

¹Computational Biology & Biomedical Informatics Program, Yale University, New Haven, CT, USA.

Biorxiv : the Preprint Server for Biology

|February 23, 2026

Summary

This summary is machine-generated.

MOSAIC is a new spectral framework for analyzing population-scale single-cell multi-omics data. It reveals hidden regulatory network changes and identifies novel cell subtypes, advancing our understanding of health and disease.

Keywords:

Differential connectivity Patient phenotyping Patient stratification Population-scale analysis Single-cell multi-omics Spectral data integration

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Area of Science:

Genomics
Computational Biology
Systems Biology

Background:

Single-cell multi-omics data analysis faces challenges with cell-centric or feature-centric approaches.
Existing methods struggle to capture both feature relationships and inter-sample heterogeneity.

Purpose of the Study:

To present MOSAIC, a novel spectral framework for population-scale single-cell multi-omics data analysis.
To enable high-resolution joint embedding of features and samples.
To facilitate downstream analyses like differential connectivity and sample subgroup identification.

Main Methods:

MOSAIC constructs sample-specific coupling matrices capturing intra- and cross-modality feature interactions.
Spectral decomposition projects these matrices into a shared latent space for joint embedding.
Differential Connectivity (DC) analysis and module isolation are key downstream applications.

Main Results:

MOSAIC identified rewiring of proliferation programs in T cells post-vaccination, revealing STAT5B functional shifts.
Analysis of HIV+ prefrontal cortex data uncovered a novel stress-driven neuronal subtype.
The framework demonstrated its ability to detect regulatory network changes independent of expression levels.

Conclusions:

MOSAIC offers a general-purpose framework for systems-level phenotypic characterization.
It provides novel biological insights from population-scale multi-omic studies.
The method enhances understanding of molecular variation in human health and disease.