An integrated cell atlas of the human lung in health and disease

single-cell
rna-seq
lung
atlas
Authors

Lisa Sikkema

Daniel C Strobl

Luke Zappia

Elo Madissoon

Nikolay S Markov

Laure-Emmanuelle Zaragosi

Meshal Ansari

Marie-Jeanne Arguel

Leonie Apperloo

Christophe Becavin

Marijn Berg

Evgeny Chichelnitskiy

Mei-I Chung

Antoine Collin

Aurore C A Gay

Baharak Hooshiar Kashani

Manu Jain

Theodore Kapellos

Tessa M Kole

Christoph H Mayr

Michael von Papen

Lance Peter

Ciro Ramirez-Suastegui

Janine Schniering

Chase J Taylor

Thomas Walzthoeni

Chuan Xu

Linh T Bui

Carlo de Donno

Leander Dony

Minzhe Guo

Austin J Gutierrez

Lukas Heumos

Ni Huang

Ignacio L Ibarra

Nathan D Jackson

Preetish Kadur Lakshminarasimha Murthy

Mohammad Lotfollahi

Tracy Tabib

Carlos Talavera-Lopez

Kyle J Travaglini

Anna Wilbrey-Clark

Kaylee B Worlock

Masahiro Yoshida

Tushar J Desai

Oliver Eickelberg

Christine Falk

Naftali Kaminski

Mark A Krasnow

Robert Lafyatis

Marko Z Nikoli

Joseph E Powell

Jayaraj Rajagopal

Orit Rozenblatt-Rosen

Max A Seibold

Dean Sheppard

Douglas P Shepherd

Sarah A Teichmann

Alexander M Tsankov

Jeffrey Whitsett

Yan Xu

Nicholas E Banovich

Pascal Barbry

Thu E Duong

Kerstin B Meyer

Jonathan A Kropski

Dana Pe’er

Herbert B Schiller

Purushothama Rao Tata

Joachim L Schultze

Alexander V Misharin

Martijn C Nawijn

Malte D Luecken

Fabian J Theis

Date

March 11, 2022

Links
Citation stats
Abstract

Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.

Citation

BibTeX citation:
@misc{sikkema2022,
  author = {Lisa Sikkema and Daniel C Strobl and Luke Zappia and Elo
    Madissoon and Nikolay S Markov and Laure-Emmanuelle Zaragosi and
    Meshal Ansari and Marie-Jeanne Arguel and Leonie Apperloo and
    Christophe Becavin and Marijn Berg and Evgeny Chichelnitskiy and
    Mei-I Chung and Antoine Collin and Aurore C A Gay and Baharak
    Hooshiar Kashani and Manu Jain and Theodore Kapellos and Tessa M
    Kole and Christoph H Mayr and Michael von Papen and Lance Peter and
    Ciro Ramirez-Suastegui and Janine Schniering and Chase J Taylor and
    Thomas Walzthoeni and Chuan Xu and Linh T Bui and Carlo de Donno and
    Leander Dony and Minzhe Guo and Austin J Gutierrez and Lukas Heumos
    and Ni Huang and Ignacio L Ibarra and Nathan D Jackson and Preetish
    Kadur Lakshminarasimha Murthy and Mohammad Lotfollahi and Tracy
    Tabib and Carlos Talavera-Lopez and Kyle J Travaglini and Anna
    Wilbrey-Clark and Kaylee B Worlock and Masahiro Yoshida and Tushar J
    Desai and Oliver Eickelberg and Christine Falk and Naftali Kaminski
    and Mark A Krasnow and Robert Lafyatis and Marko Z Nikoli and Joseph
    E Powell and Jayaraj Rajagopal and Orit Rozenblatt-Rosen and Max A
    Seibold and Dean Sheppard and Douglas P Shepherd and Sarah A
    Teichmann and Alexander M Tsankov and Jeffrey Whitsett and Yan Xu
    and Nicholas E Banovich and Pascal Barbry and Thu E Duong and
    Kerstin B Meyer and Jonathan A Kropski and Dana Pe’er and Herbert B
    Schiller and Purushothama Rao Tata and Joachim L Schultze and
    Alexander V Misharin and Martijn C Nawijn and Malte D Luecken and
    Fabian J Theis},
  title = {An Integrated Cell Atlas of the Human Lung in Health and
    Disease},
  date = {2022-03-11},
  url = {https://lazappi.id.au/publications/2022-sikkema-HLCA},
  doi = {10.1101/2022.03.10.483747},
  langid = {en},
  abstract = {Organ- and body-scale cell atlases have the potential to
    transform our understanding of human biology. To capture the
    variability present in the population, these atlases must include
    diverse demographics such as age and ethnicity from both healthy and
    diseased individuals. The growth in both size and number of
    single-cell datasets, combined with recent advances in computational
    techniques, for the first time makes it possible to generate such
    comprehensive large-scale atlases through integration of multiple
    datasets. Here, we present the integrated Human Lung Cell Atlas
    (HLCA) combining 46 datasets of the human respiratory system into a
    single atlas spanning over 2.2 million cells from 444 individuals
    across health and disease. The HLCA contains a consensus
    re-annotation of published and newly generated datasets, resolving
    under- or misannotation of 59\% of cells in the original datasets.
    The HLCA enables recovery of rare cell types, provides consensus
    marker genes for each cell type, and uncovers gene modules
    associated with demographic covariates and anatomical location
    within the respiratory system. To facilitate the use of the HLCA as
    a reference for single-cell lung research and allow rapid analysis
    of new data, we provide an interactive web portal to project
    datasets onto the HLCA. Finally, we demonstrate the value of the
    HLCA reference for interpreting disease-associated changes. Thus,
    the HLCA outlines a roadmap for the development and use of
    organ-scale cell atlases within the Human Cell Atlas.}
}
For attribution, please cite this work as:
Lisa Sikkema, Daniel C Strobl, Luke Zappia, Elo Madissoon, Nikolay S Markov, Laure-Emmanuelle Zaragosi, Meshal Ansari, et al. 2022. “An Integrated Cell Atlas of the Human Lung in Health and Disease.” bioRxiv. https://doi.org/10.1101/2022.03.10.483747.