Predicting trajectories of illness using RNA velocity of whole blood
Abstract
Abstract Transcriptomic analyses reveal the status of cells, tissues, or organisms, across states of health and disease. RNA velocity adds a temporal dimension to single cell analyses, predicting future transcriptomic and phenotypic states, based on the current spliced and unspliced mRNA of each cell. We hypothesized that RNA velocity could be adapted to predict future clinical state of individuals with acute and chronic illnesses, using their whole-blood transcriptomes. We developed VeloCD, a method for quantitative prediction of transitions in clinical state from a single time-point RNA sample. This predicts transcriptomic trajectories and future infection status in influenza A and SARS-CoV-2 controlled human infection studies, which are consistent with trajectories in naturally acquired infections. In HIV-TB coinfected individuals, VeloCD predicts the onset of immune reconstitution inflammatory syndrome. In individuals receiving biological therapy for inflammatory bowel disease, whole blood RNA velocity after the first dose of treatment indicates whether remission will be achieved by the end of the treatment course. In a multinational observational study of acutely unwell febrile children, VeloCD predicts those with greatest medical care requirements. Our results demonstrate proof-of-concept for the use of RNA velocity to predict trajectories of human diseases.
Article Details
Authors (306)
Claire Dunican
Clare Wilson
Dominic Habgood-Coote
Suzanna Paterson
Mahdad Noursadeghi
Raymond Moseki
Cari Stek
Robert J. Wilkinson
Philipp K. A. Agyeman
Coco R. Beudeker
Giske Biesbroek
Karen Brengel-Pesce
Enitan D. Carrol
Lachlan J. M. Coin
Giselle D’Souza
Tisham De
Marieke Emonts
Katy Fidler
Colin G. Fink
Ioanna Georgaki
Laura Kolberg
Mojca Kolnik
Taco Kuijpers
Federico Martinón-Torres
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Marine Mommert-Tripon
Samuel Nichols
Stephane Paulus
Marko Pokorn
Andrew J. Pollard
Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom
Irene Rivero-Calle
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Luregn J. Schlapbach
Nina A. Schweintzger
Ching-Fen Shen
Shrijana Shrestha
Chantal D. Tan
Maria Tsolia
National and Kapodistrian University of Athens, Athens
Effua Usuf
Clementien L. Vermont
Marie Voice
Shunmay Yeung
Dace Zavadska
Werner Zenz
Victoria J. Wright
Michael Levin
Jethro Herberg
Lucas Baumard
Evangelos Bellos
Rachel Galassini
Shea Hamilton
Clive Hoggart
Sara Hourmat
Heather Jackson
Naomi Lin
Ian Maconochie
Stephanie Menikou
Ruud Nijman
Ivonne Pena Paz
Oliver Powell
Priyen Shah
Ortensia Vito
Molly Stevens
Eunjung Kim
Nayoung Kim
Physics of Fluids Department, Faculty of Science and Technology, Max Planck Center Twente for Complex Fluid Dynamics, University of Twente
Amina Abdulla
Ladan Ali
Sarah Darnell
Rikke Jorgensen
Sobia Mustafa
Salina Persand
Julia Dudley
Vivien Richmond
Emma Tagliavini
Elizabeth Cocklin
Rebecca Jennings
Joanne Johnston
Aakash Khanijau
Simon Leigh
Nadia Lewis-Burke
Karen Newall
Sam Romaine
Rama Kandasamy
Michael J. Carter
Daniel O’Connor
Sagida Bibi
Dominic F. Kelly
Meeru Gurung
Stephen Thorson
Imran Ansari
David R. Murdoch
Zoe Oliver
Emma Lim
Lucille Valentine
Karen Allen
Kathryn Bell
Adora Chan
Stephen Crulley
Kirsty Devine
Daniel Fabian
Sharon King
Paul McAlinden
Sam McDonald
Anne McDonnell
Ailsa Pickering
Evelyn Thomson
Amanda Wood
Diane Wallia
Phil Woodsford
Frances Baxter
Ashley Bell
Mathew Rhodes
Rachel Agbeko
Christine Mackerness
Bryan Baas
Lieke Kloosterhuis
Wilma Oosthoek
Tasnim Arif
Joshua Bennet
Kalvin Collings
Ilona van der Giessen
Alex Martin
Aqeela Rashid
Emily Rowlands
Gabriella de Vries
Fabian van der Velden
Joshua Soon
Mike Martin
Ravi Mistry
Juan Emmanuel Dewez
Martin Hibberd
David Bath
Alec Miners
Elizabeth Fitchett
Leo Calvo-Bado
Antonio Salas
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Fernando Álvez González
Cristina Balo Farto
Ruth Barral-Arca
María Barreiro Castro
Xabier Bello
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Mirian Ben García
Sandra Carnota
Miriam Cebey-López
María José Curras-Tuala
Carlos Durán Suárez
Luisa García Vicente
Alberto Gómez-Carballa
Jose Gómez Rial
Pilar Leboráns Iglesias
Nazareth Martinón-Torres
José María Martinón Sánchez
Belén Mosquera Pérez
Jacobo Pardo-Seco
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Lidia Piñeiro Rodríguez
Sara Pischedda
Sara Rey Vázquez
Irene Rivero Calle
Carmen Rodríguez-Tenreiro
Lorenzo Redondo-Collazo
Miguel Sadiki Ora
Sonia Serén Fernández
Cristina Serén Trasorras
Marisol Vilas Iglesias
Henriëtte A. Moll
Dorine M. Borensztajn
Nienke N. Hagedoorn
Joany Zachariasse
W. Dik
Michiel van der Flier
Ronald de Groot
Marien I. de Jonge
Koen van Aerde
Wynand Alkema
Bryan van den Broek
Jolein Gloerich
Alain J. van Gool
Stefanie Henriet
Martijn Huijnen
Ria Philipsen
Esther Willems
G. P. J. M. Gerrits
M. van Leur
J. Heidema
L. de Haan
C. J. Miedema
C. Neeleman
C. C. Obihara
G. A. Tramper-Stranders
Ilse Jongerius
J. M. van den Berg
D. Schonenberg
A. M. Barendregt
D. Pajkrt
M. van der Kuip
A. M. van Furth
Evelien Sprenkeler
Judith Zandstra
G. van Mierlo
J. Geissler
Anda Balode
Arta Bārzdiņa
Dārta Deksne
Dace Gardovska
Dagne Grāvele
Ilze Grope
Anija Meiere
Ieva Nokalna
Jana Pavāre
Zanda Pučuka
Katrīna Selecka
Aleksandra Rudzate
Dace Svile
Urzula Nora Urbāne
Benno Kohlmaier
Manfred G. Sagmeister
Daniela S. Kohlfürst
Christoph Zurl
Alexander Binder
Susanne Hösele
Manuel Leitner
Lena Pölz
Glorija Rajic
Sebastian Bauchinger
Hinrich Baumgart
Martin Benesch
Astrid Ceolotto
Ernst Eber
Siegfried Gallistl
Gunther Gores
Harald Haidl
Almuthe Hauer
Christa Hude
Markus Keldorfer
Larissa Krenn
Heidemarie Pilch
Andreas Pfleger
Klaus Pfurtscheller
Gudrun Nordberg
Tobias Niedrist
Siegfried Rödl
Andrea Skrabl-Baumgartner
Matthias Sperl
Laura Stampfer
Volker Strenger
Holger Till
Andreas Trobisch
Sabine Löffler
Ulrich von Both
Manuela Zwerenz
Judith Buschbeck
Christoph Bidlingmaier
Vera Binder
Katharina Danhauser
Nikolaus Haas
Matthias Griese
Tobias Feuchtinger
Julia Keil
Matthias Kappler
Eberhard Lurz
Georg Muench
Karl Reiter
Carola Schoen
Irini Eleftheriou
Maria Tambouratzi
Antonis Marmarinos
Marietta Xagorari
Kelly Syggelou
Christoph Aebi
Verena Wyss
Mariama Usman
Eric Giannoni
Martin Stocker
Klara M. Posfay-Barbe
Ulrich Heininger
Sara Bernhard-Stirnemann
Anita Niederer-Loher
Christian Kahlert
Giancarlo Natalucci
Christa Relly
Thomas Riedel
Christoph Berger
Katarina Vincek
Tina Plankar Srovin
Natalija Bahovec
Petra Prunk
Veronika Osterman
Tanja Avramoska
François Mallet
Alexandre Pachot
Kalifa Bojang
Syed M. A. Zaman
Fatou Secka
Suzanne Anderson
Anna Roca
Isatou Sarr
Momodou Saidykhan
Saffiatou Darboe
Samba Ceesay
Umberto D’Alessandro
Ching-Chuan Liu
Shih-Min Wang
Rachel P. J. Lai
Graeme Meintjes
Department of Medicine, University of Cape Town, Cape Town, South Africa
Christopher Chiu
Mauricio Barahona
Department of Mathematics, Imperial College London , London SW7 2AZ,
Myrsini Kaforou
Aubrey J. Cunnington