TrAGEDy-trajectory alignment of gene expression dynamics.

Ross F Laidlaw, Emma M Briggs, Keith R Matthews, Amir Madany Mamlouk, Richard McCulloch, Thomas D Otto
Author Information
  1. Ross F Laidlaw: Centre for Parasitology, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
  2. Emma M Briggs: Centre for Parasitology, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
  3. Keith R Matthews: Institute for Immunology and Infection Research, University of Edinburgh, Edinburgh, EH8 9YL, United Kingdom.
  4. Amir Madany Mamlouk: Institute for Neuro- and Bioinformatics, University of L��beck, L��beck, 23562, Germany.
  5. Richard McCulloch: Centre for Parasitology, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. ORCID
  6. Thomas D Otto: Centre for Parasitology, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. ORCID

Abstract

MOTIVATION: Single-cell transcriptomics sequencing is used to compare different biological processes. However, often, those processes are asymmetric which are difficult to integrate. Current approaches often rely on integrating samples from each condition before either cluster-based comparisons or analysis of an inferred shared trajectory.
RESULTS: We present Trajectory Alignment of Gene Expression Dynamics (TrAGEDy), which allows the alignment of independent trajectories to avoid the need for error-prone integration steps. Across simulated datasets, TrAGEDy returns the correct underlying alignment of the datasets, outperforming current tools which fail to capture the complexity of asymmetric alignments. When applied to real datasets, TrAGEDy captures more biologically relevant genes and processes, which other differential expression methods fail to detect when looking at the developments of T cells and the bloodstream forms of Trypanosoma brucei when affected by genetic knockouts.
AVAILABILITY AND IMPLEMENTATION: TrAGEDy is freely available at https://github.com/No2Ross/TrAGEDy, and implemented in R.

Grants

  1. MR/N013166/1/Medical Research Council
  2. 218648/Z/19/Z/Wellcome Trust
  3. BB/R017166/1/BBSRC Project
  4. ANR-21-EXES-0005/ExposUM Institute of the University of Montpellier
  5. /Occitanie Region

MeSH Term

Software
Gene Expression Profiling
Trypanosoma brucei brucei
Single-Cell Analysis
Algorithms
Transcriptome
Computational Biology

Word Cloud

Created with Highcharts 10.0.0TrAGEDyprocessesalignmentdatasetsoftenasymmetricfailexpressionMOTIVATION:Single-celltranscriptomicssequencingusedcomparedifferentbiologicalHoweverdifficultintegrateCurrentapproachesrelyintegratingsamplesconditioneithercluster-basedcomparisonsanalysisinferredsharedtrajectoryRESULTS:presentTrajectoryAlignmentGeneExpressionDynamicsallowsindependenttrajectoriesavoidneederror-proneintegrationstepsAcrosssimulatedreturnscorrectunderlyingoutperformingcurrenttoolscapturecomplexityalignmentsappliedrealcapturesbiologicallyrelevantgenesdifferentialmethodsdetectlookingdevelopmentsTcellsbloodstreamformsTrypanosomabruceiaffectedgeneticknockoutsAVAILABILITYANDIMPLEMENTATION:freelyavailablehttps://githubcom/No2Ross/TrAGEDyimplementedRTrAGEDy-trajectorygenedynamics

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