Awesome Repeated Measures "omics" Analysis

A community-maintained list of software packages for analysis of longitudinal/repeated measures studies utilizing high-dimensional "omics" data.

While many of the packages here are marketed for a single type of "omics" data (metagenomics, metabolome, etc.). Many can be utilized across the -omics universe.

The common thread among the methods listed here is that the same samples are measured across multiple time-points and may be measured with two or more modalities (e.g.: microbiome, metabolome, and miRNA). The data can be described as multiple matrices/tables with the same number of samples (not a strict requirement for all methods), a varying number of features, and (in some cases) clinical/environmental/other covariates of interest.

The repo is in the style of Mike Love's awesome-multi-omics repository for multi-omics analysis methods (which, in turn, is in the style of Sean Davis' awesome-single-cell repo for single-cell analysis methods). Note that there is a Multi-omics section for software handling repeated measures studies with multiple measurement modalities, so there will be some overlap with awesome-multi-omics.

Contributions are welcome and encouraged. I can't read all the papers by myself.

For brevity, entries for software and scientific articles only list the last name of the first author.

NOTE: Entries with ** before the year are non-peer reviewed preprints.

Software packages and methods

Spline Modeling

• 2015 - Straube - A Linear Mixed Model Spline Framework for Analysing Time Course ‘Omics’ Data
• 2017 - metaDprof - Luo - An informative approach on differential abundance analysis for time-course metagenomic sequencing data
• 2018 - SplinectomeR - Shields-Cutler - SplinectomeR Enables Group Comparisons in Longitudinal Microbiome Studies
• 2018 - MetaLonDA - Metwally - MetaLonDA: a flexible R package for identifying time intervals of differentially abundant features in metagenomic longitudinal studies - vignette

Linear/Mixed Modeling

• 2016 - ZIBR - Chen - zero-inflated Beta regression - A two-part mixed-effects model for analyzing longitudinal microbiome compositional data
• 2018 - LassoGLMMforMicrobiomes - Tipton - lasso-penalized generalized linear mixed model (LassoGLMM) with variable selection - Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model
• 2018 - MALLARD - Silverman - Dynamic linear models guide design and analysis of microbiota studies within artificial human guts
• 2019 - BEEM - Li - An expectation-maximization algorithm enables accurate ecological modeling using longitudinal microbiome sequencing data
• 2019 - (a)GLMM-MiRKAT - Koh - A Distance-Based Kernel Association Test Based on the Generalized Linear Mixed Model for Correlated Microbiome Studies
• 2020 - NBZIMM - Zhang - NBZIMM: negative binomial and zero-inflated mixed models, with application to microbiome/metagenomics data analysis - vignette
• 2020 - Zhang - Fast zero-inflated negative binomial mixed modeling approach for analyzing longitudinal metagenomics data
• 2021 - MaAsLin 2 - Mallick - Multivariable association discovery in population-scale meta-omics studies - vignette
• 2022 - MiRKAT-MC - Jiang - MiRKAT-MC: A Distance-Based Microbiome Kernel Association Test With Multi-Categorical Outcomes - vignette
• 2023 - coda4microbiome - Calle - coda4microbiome: compositional data analysis for microbiome cross-sectional and longitudinal studies

Multi-level Modeling

• 2012 - mixOmics - Liquet - A novel approach for biomarker selection and the integration of repeated measures experiments from two assays

Bayesian Modeling

• 2015 - BioMiCo - Shafiei - BioMiCo: a supervised Bayesian model for inference of microbial community structure

Stochastic/Probabilistic Modeling

• 2018 - TGP-CODA - Äijö - Temporal probabilistic modeling of bacterial compositions derived from 16S rRNA sequencing
• 2020 - LUMINATE - Joseph - Efficient and Accurate Inference of Mixed Microbial Population Trajectories from Longitudinal Count Data

Graph/Network Methods

• 2011 - eLSA - Xia - Extended local similarity analysis (eLSA) of microbial community and other time series data with replicates
• 2018 - Coenen - Limitations of Correlation-Based Inference in Complex Virus-Microbe Communities
• 2019 - Ai - bivariate autoregressive model with Granger causality - Constructing the Microbial Association Network from large-scale time series data using Granger causality
• 2019 - Zhang - data driven local similarity analysis - Statistical significance approximation for local similarity analysis of dependent time series data
• 2019 - Ai - Explore mediated co-varying dynamics in microbial community using integrated local similarity and liquid association analysis
• 2023 - Melnyk - Understanding microbiome dynamics via interpretable graph representation learning

Machine Learning/Artificial Neural Networks (Deep Learning) Methods

• 2019 - DIVERS - Ji - Quantifying spatiotemporal variability and noise in absolute microbiota abundances using replicate sampling
• 2021 - phyLoSTM - Sharma - combined modeling using CNN for feature extraction and LSTM for temporal dependency analysis - phyLoSTM: a novel deep learning model on disease prediction from longitudinal microbiome data
• 2023 - Hu - A review on longitudinal data analysis with random forest

Tensor decomposition/factorization Methods

• 2023 - EMBED - Shahin - EMBED: Essential MicroBiomE Dynamics, a dimensionality reduction approach for longitudinal microbiome studies
• ** 2024 - TEMPTED - Shi - Time-Informed Dimensionality Reduction for Longitudinal Microbiome Studies

Ecology Literature

• 2011 - Lindenmayer - Cross-sectional vs. longitudinal research: a case study of trees with hollows and marsupials in Australian forests
• 2019 - pldist - Plantinga - pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis
• 2019 - McGeoch - Measuring continuous compositional change using decline and decay in zeta diversity
• 2019 - Buckley - Multivariate methods for testing hypotheses of temporal community dynamics - paper 2
• 2020 - Yang - Toward a more temporally explicit framework for community ecology

Phylogeny-based

• 2020 - Darcy - A phylogenetic model for the recruitment of species into microbial communities and application to studies of the human microbiome

Causal Effect Estimation

Some are not technically longitudinal, but heading in that direction and good to know about.

• 2016 - Bind - generalized mixed-effects models - Causal mediation analysis for longitudinal data with exogenous exposure
• 2020 - SparseMCMM - Wang - linear log-contrast regression/Dirichlet regression - Estimating and testing the microbial causal mediation effect with high-dimensional and compositional microbiome data
• 2022 - CMMB - Sohn - A compositional mediation model for a binary outcome: Application to microbiome studies
• 2023 - SparseMCMM_HD - - A microbial causal mediation analytic tool for health disparity and applications in body mass index

Pathway Analysis

• 2012 - DIA - Bionaz - A Novel Dynamic Impact Approach (DIA) for Functional Analysis of Time-Course Omics Studies
• 2016 - Du - A decision analysis model for KEGG pathway analysis

Longitudinal Multi-omics Integration

• 2019 - timeOmics - Bodein - A Generic Multivariate Framework for the Integration of Microbiome Longitudinal Studies With Other Data Types vignette
• 2019 - DIABLO - Singh - Multi-block Sparse PLS-Discriminant Analysis - DIABLO: an integrative approach for identifying key molecular drivers from multi-omics assays
  • Does not directly handle repeated measures, but can after some preprocessing.
• 2020 - PyIOmica - Domanskyi - PyIOmica: longitudinal omics analysis and trend identification
• 2022 - MEFISTO - Velten - Identifying temporal and spatial patterns of variation from multi-modal data using MEFISTO - vignette
• 2023 - PALMO - Vasaikar - A comprehensive platform for analyzing longitudinal multi-omics data

Data Simulation

• ** 2022 - MTIST - Hussey - The MTIST platform: a microbiome time series inference standardized test simulation, dataset, and scoring systems
• ** 2024 - SimMiL - Weaver & Hendricks - SimMiL: Simulating Microbiome Longitudinal Data

Reviews / Evaluations / Opinion

• 2017 - Liang - Dynamic modeling and network approaches for omics time course data: overview of computational approaches and applications
• ** 2018 - Silverman - Statistical Considerations in the Design and Analysis of Longitudinal Microbiome Studies
• 2018 - Liang - Dynamic modeling and network approaches for omics time course data
• ** 2019 - Buckley - Multivariate methods for testing hypotheses of temporal community dynamics
• 2021 - Lv - Causal Inference in Microbiome Medicine: Principles and Applications
• 2022 - Corander - Causal discovery for the microbiome
• 2022 - Kodikara - Statistical challenges in longitudinal microbiome data analysis
• 2023 - Grieneisen - How longitudinal data can contribute to our understanding of host genetic effects on the gut microbiome
• 2023 - Hu & Szymczak - A review on longitudinal data analysis with random forest
• 2024 - Lyu - Methodological Considerations in Longitudinal Analyses of Microbiome Data: A Comprehensive Review

Longitudinal/Repeated Measures Application Papers

• 2021 - Duran-Pinedo - Long-term dynamics of the human oral microbiome during clinical disease progression
• 2022 - Armoni - Temporal Alignment of Longitudinal Microbiome Data
• 2022 - Murillo - Assessing the drivers of gut microbiome composition in wild redfronted lemurs via longitudinal metacommunity analysis

Meetings and workshops