Predicting trajectories of illness using RNA velocity of whole blood

C Claire Dunican C Clare Wilson D Dominic Habgood-Coote S Suzanna Paterson M Mahdad Noursadeghi R Raymond Moseki C Cari Stek R Robert J. Wilkinson P Philipp K. A. Agyeman C Coco R. Beudeker G Giske Biesbroek K Karen Brengel-Pesce E Enitan D. Carrol L Lachlan J. M. Coin G Giselle D’Souza T Tisham De M Marieke Emonts K Katy Fidler C Colin G. Fink I Ioanna Georgaki L Laura Kolberg M Mojca Kolnik T Taco Kuijpers F Federico Martinón-Torres (Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain) M Marine Mommert-Tripon S Samuel Nichols S Stephane Paulus M Marko Pokorn A Andrew J. Pollard (Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom) I Irene Rivero-Calle (Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain) L Luregn J. Schlapbach N Nina A. Schweintzger C Ching-Fen Shen S Shrijana Shrestha C Chantal D. Tan M Maria Tsolia (National and Kapodistrian University of Athens, Athens) E Effua Usuf C Clementien L. Vermont M Marie Voice S Shunmay Yeung D Dace Zavadska W Werner Zenz V Victoria J. Wright M Michael Levin J Jethro Herberg L Lucas Baumard E Evangelos Bellos R Rachel Galassini S Shea Hamilton C Clive Hoggart S Sara Hourmat H Heather Jackson N Naomi Lin I Ian Maconochie S Stephanie Menikou R Ruud Nijman I Ivonne Pena Paz O Oliver Powell P Priyen Shah O Ortensia Vito M Molly Stevens E Eunjung Kim N Nayoung Kim (Physics of Fluids Department, Faculty of Science and Technology, Max Planck Center Twente for Complex Fluid Dynamics, University of Twente) A Amina Abdulla L Ladan Ali S Sarah Darnell R Rikke Jorgensen S Sobia Mustafa S Salina Persand J Julia Dudley V Vivien Richmond E Emma Tagliavini E Elizabeth Cocklin R Rebecca Jennings J Joanne Johnston A Aakash Khanijau S Simon Leigh N Nadia Lewis-Burke K Karen Newall S Sam Romaine R Rama Kandasamy M Michael J. Carter D Daniel O’Connor S Sagida Bibi D Dominic F. Kelly M Meeru Gurung S Stephen Thorson I Imran Ansari D David R. Murdoch Z Zoe Oliver E Emma Lim L Lucille Valentine K Karen Allen K Kathryn Bell A Adora Chan S Stephen Crulley K Kirsty Devine D Daniel Fabian S Sharon King P Paul McAlinden S Sam McDonald A Anne McDonnell A Ailsa Pickering E Evelyn Thomson A Amanda Wood D Diane Wallia P Phil Woodsford F Frances Baxter A Ashley Bell M Mathew Rhodes R Rachel Agbeko C Christine Mackerness B Bryan Baas L Lieke Kloosterhuis W Wilma Oosthoek T Tasnim Arif J Joshua Bennet K Kalvin Collings I Ilona van der Giessen A Alex Martin A Aqeela Rashid E Emily Rowlands G Gabriella de Vries F Fabian van der Velden J Joshua Soon M Mike Martin R Ravi Mistry J Juan Emmanuel Dewez M Martin Hibberd D David Bath A Alec Miners E Elizabeth Fitchett L Leo Calvo-Bado A Antonio Salas (Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain) F Fernando Álvez González C Cristina Balo Farto R Ruth Barral-Arca M María Barreiro Castro X Xabier Bello (Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain) M Mirian Ben García S Sandra Carnota M Miriam Cebey-López M María José Curras-Tuala C Carlos Durán Suárez L Luisa García Vicente A Alberto Gómez-Carballa J Jose Gómez Rial P Pilar Leboráns Iglesias N Nazareth Martinón-Torres J José María Martinón Sánchez B Belén Mosquera Pérez J Jacobo Pardo-Seco (Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain) L Lidia Piñeiro Rodríguez S Sara Pischedda S Sara Rey Vázquez I Irene Rivero Calle C Carmen Rodríguez-Tenreiro L Lorenzo Redondo-Collazo M Miguel Sadiki Ora S Sonia Serén Fernández C Cristina Serén Trasorras M Marisol Vilas Iglesias H Henriëtte A. Moll D Dorine M. Borensztajn N Nienke N. Hagedoorn J Joany Zachariasse W W. Dik M Michiel van der Flier R Ronald de Groot M Marien I. de Jonge K Koen van Aerde W Wynand Alkema B Bryan van den Broek J Jolein Gloerich A Alain J. van Gool S Stefanie Henriet M Martijn Huijnen R Ria Philipsen E Esther Willems G G. P. J. M. Gerrits M M. van Leur J J. Heidema L L. de Haan C C. J. Miedema C C. Neeleman C C. C. Obihara G G. A. Tramper-Stranders I Ilse Jongerius J J. M. van den Berg D D. Schonenberg A A. M. Barendregt D D. Pajkrt M M. van der Kuip A A. M. van Furth E Evelien Sprenkeler J Judith Zandstra G G. van Mierlo J J. Geissler A Anda Balode A Arta Bārzdiņa D Dārta Deksne D Dace Gardovska D Dagne Grāvele I Ilze Grope A Anija Meiere I Ieva Nokalna J Jana Pavāre Z Zanda Pučuka K Katrīna Selecka A Aleksandra Rudzate D Dace Svile U Urzula Nora Urbāne B Benno Kohlmaier M Manfred G. Sagmeister D Daniela S. Kohlfürst C Christoph Zurl A Alexander Binder S Susanne Hösele M Manuel Leitner L Lena Pölz G Glorija Rajic S Sebastian Bauchinger H Hinrich Baumgart M Martin Benesch A Astrid Ceolotto E Ernst Eber S Siegfried Gallistl G Gunther Gores H Harald Haidl A Almuthe Hauer C Christa Hude M Markus Keldorfer L Larissa Krenn H Heidemarie Pilch A Andreas Pfleger K Klaus Pfurtscheller G Gudrun Nordberg T Tobias Niedrist S Siegfried Rödl A Andrea Skrabl-Baumgartner M Matthias Sperl L Laura Stampfer V Volker Strenger H Holger Till A Andreas Trobisch S Sabine Löffler U Ulrich von Both M Manuela Zwerenz J Judith Buschbeck C Christoph Bidlingmaier V Vera Binder K Katharina Danhauser N Nikolaus Haas M Matthias Griese T Tobias Feuchtinger J Julia Keil M Matthias Kappler E Eberhard Lurz G Georg Muench K Karl Reiter C Carola Schoen I Irini Eleftheriou M Maria Tambouratzi A Antonis Marmarinos M Marietta Xagorari K Kelly Syggelou C Christoph Aebi V Verena Wyss M Mariama Usman E Eric Giannoni M Martin Stocker K Klara M. Posfay-Barbe U Ulrich Heininger S Sara Bernhard-Stirnemann A Anita Niederer-Loher C Christian Kahlert G Giancarlo Natalucci C Christa Relly T Thomas Riedel C Christoph Berger K Katarina Vincek T Tina Plankar Srovin N Natalija Bahovec P Petra Prunk V Veronika Osterman T Tanja Avramoska F François Mallet A Alexandre Pachot K Kalifa Bojang S Syed M. A. Zaman F Fatou Secka S Suzanne Anderson A Anna Roca I Isatou Sarr M Momodou Saidykhan S Saffiatou Darboe S Samba Ceesay U Umberto D’Alessandro C Ching-Chuan Liu S Shih-Min Wang R Rachel P. J. Lai G Graeme Meintjes (Department of Medicine, University of Cape Town, Cape Town, South Africa) C Christopher Chiu M Mauricio Barahona (Department of Mathematics, Imperial College London , London SW7 2AZ,) M Myrsini Kaforou A Aubrey J. Cunnington

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

Volume / Issue Vol. 17, Issue 1
Published May 06, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (306)

C

Claire Dunican

C

Clare Wilson

D

Dominic Habgood-Coote

S

Suzanna Paterson

M

Mahdad Noursadeghi

R

Raymond Moseki

C

Cari Stek

R

Robert J. Wilkinson

P

Philipp K. A. Agyeman

C

Coco R. Beudeker

G

Giske Biesbroek

K

Karen Brengel-Pesce

E

Enitan D. Carrol

L

Lachlan J. M. Coin

G

Giselle D’Souza

T

Tisham De

M

Marieke Emonts

K

Katy Fidler

C

Colin G. Fink

I

Ioanna Georgaki

L

Laura Kolberg

M

Mojca Kolnik

T

Taco Kuijpers

F

Federico Martinón-Torres

Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain

M

Marine Mommert-Tripon

S

Samuel Nichols

S

Stephane Paulus

M

Marko Pokorn

A

Andrew J. Pollard

Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

I

Irene Rivero-Calle

Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain

L

Luregn J. Schlapbach

N

Nina A. Schweintzger

C

Ching-Fen Shen

S

Shrijana Shrestha

C

Chantal D. Tan

M

Maria Tsolia

National and Kapodistrian University of Athens, Athens

E

Effua Usuf

C

Clementien L. Vermont

M

Marie Voice

S

Shunmay Yeung

D

Dace Zavadska

W

Werner Zenz

V

Victoria J. Wright

M

Michael Levin

J

Jethro Herberg

L

Lucas Baumard

E

Evangelos Bellos

R

Rachel Galassini

S

Shea Hamilton

C

Clive Hoggart

S

Sara Hourmat

H

Heather Jackson

N

Naomi Lin

I

Ian Maconochie

S

Stephanie Menikou

R

Ruud Nijman

I

Ivonne Pena Paz

O

Oliver Powell

P

Priyen Shah

O

Ortensia Vito

M

Molly Stevens

E

Eunjung Kim

N

Nayoung Kim

Physics of Fluids Department, Faculty of Science and Technology, Max Planck Center Twente for Complex Fluid Dynamics, University of Twente

A

Amina Abdulla

L

Ladan Ali

S

Sarah Darnell

R

Rikke Jorgensen

S

Sobia Mustafa

S

Salina Persand

J

Julia Dudley

V

Vivien Richmond

E

Emma Tagliavini

E

Elizabeth Cocklin

R

Rebecca Jennings

J

Joanne Johnston

A

Aakash Khanijau

S

Simon Leigh

N

Nadia Lewis-Burke

K

Karen Newall

S

Sam Romaine

R

Rama Kandasamy

M

Michael J. Carter

D

Daniel O’Connor

S

Sagida Bibi

D

Dominic F. Kelly

M

Meeru Gurung

S

Stephen Thorson

I

Imran Ansari

D

David R. Murdoch

Z

Zoe Oliver

E

Emma Lim

L

Lucille Valentine

K

Karen Allen

K

Kathryn Bell

A

Adora Chan

S

Stephen Crulley

K

Kirsty Devine

D

Daniel Fabian

S

Sharon King

P

Paul McAlinden

S

Sam McDonald

A

Anne McDonnell

A

Ailsa Pickering

E

Evelyn Thomson

A

Amanda Wood

D

Diane Wallia

P

Phil Woodsford

F

Frances Baxter

A

Ashley Bell

M

Mathew Rhodes

R

Rachel Agbeko

C

Christine Mackerness

B

Bryan Baas

L

Lieke Kloosterhuis

W

Wilma Oosthoek

T

Tasnim Arif

J

Joshua Bennet

K

Kalvin Collings

I

Ilona van der Giessen

A

Alex Martin

A

Aqeela Rashid

E

Emily Rowlands

G

Gabriella de Vries

F

Fabian van der Velden

J

Joshua Soon

M

Mike Martin

R

Ravi Mistry

J

Juan Emmanuel Dewez

M

Martin Hibberd

D

David Bath

A

Alec Miners

E

Elizabeth Fitchett

L

Leo Calvo-Bado

A

Antonio Salas

Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain

F

Fernando Álvez González

C

Cristina Balo Farto

R

Ruth Barral-Arca

M

María Barreiro Castro

X

Xabier Bello

Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain

M

Mirian Ben García

S

Sandra Carnota

M

Miriam Cebey-López

M

María José Curras-Tuala

C

Carlos Durán Suárez

L

Luisa García Vicente

A

Alberto Gómez-Carballa

J

Jose Gómez Rial

P

Pilar Leboráns Iglesias

N

Nazareth Martinón-Torres

J

José María Martinón Sánchez

B

Belén Mosquera Pérez

J

Jacobo Pardo-Seco

Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain

L

Lidia Piñeiro Rodríguez

S

Sara Pischedda

S

Sara Rey Vázquez

I

Irene Rivero Calle

C

Carmen Rodríguez-Tenreiro

L

Lorenzo Redondo-Collazo

M

Miguel Sadiki Ora

S

Sonia Serén Fernández

C

Cristina Serén Trasorras

M

Marisol Vilas Iglesias

H

Henriëtte A. Moll

D

Dorine M. Borensztajn

N

Nienke N. Hagedoorn

J

Joany Zachariasse

W

W. Dik

M

Michiel van der Flier

R

Ronald de Groot

M

Marien I. de Jonge

K

Koen van Aerde

W

Wynand Alkema

B

Bryan van den Broek

J

Jolein Gloerich

A

Alain J. van Gool

S

Stefanie Henriet

M

Martijn Huijnen

R

Ria Philipsen

E

Esther Willems

G

G. P. J. M. Gerrits

M

M. van Leur

J

J. Heidema

L

L. de Haan

C

C. J. Miedema

C

C. Neeleman

C

C. C. Obihara

G

G. A. Tramper-Stranders

I

Ilse Jongerius

J

J. M. van den Berg

D

D. Schonenberg

A

A. M. Barendregt

D

D. Pajkrt

M

M. van der Kuip

A

A. M. van Furth

E

Evelien Sprenkeler

J

Judith Zandstra

G

G. van Mierlo

J

J. Geissler

A

Anda Balode

A

Arta Bārzdiņa

D

Dārta Deksne

D

Dace Gardovska

D

Dagne Grāvele

I

Ilze Grope

A

Anija Meiere

I

Ieva Nokalna

J

Jana Pavāre

Z

Zanda Pučuka

K

Katrīna Selecka

A

Aleksandra Rudzate

D

Dace Svile

U

Urzula Nora Urbāne

B

Benno Kohlmaier

M

Manfred G. Sagmeister

D

Daniela S. Kohlfürst

C

Christoph Zurl

A

Alexander Binder

S

Susanne Hösele

M

Manuel Leitner

L

Lena Pölz

G

Glorija Rajic

S

Sebastian Bauchinger

H

Hinrich Baumgart

M

Martin Benesch

A

Astrid Ceolotto

E

Ernst Eber

S

Siegfried Gallistl

G

Gunther Gores

H

Harald Haidl

A

Almuthe Hauer

C

Christa Hude

M

Markus Keldorfer

L

Larissa Krenn

H

Heidemarie Pilch

A

Andreas Pfleger

K

Klaus Pfurtscheller

G

Gudrun Nordberg

T

Tobias Niedrist

S

Siegfried Rödl

A

Andrea Skrabl-Baumgartner

M

Matthias Sperl

L

Laura Stampfer

V

Volker Strenger

H

Holger Till

A

Andreas Trobisch

S

Sabine Löffler

U

Ulrich von Both

M

Manuela Zwerenz

J

Judith Buschbeck

C

Christoph Bidlingmaier

V

Vera Binder

K

Katharina Danhauser

N

Nikolaus Haas

M

Matthias Griese

T

Tobias Feuchtinger

J

Julia Keil

M

Matthias Kappler

E

Eberhard Lurz

G

Georg Muench

K

Karl Reiter

C

Carola Schoen

I

Irini Eleftheriou

M

Maria Tambouratzi

A

Antonis Marmarinos

M

Marietta Xagorari

K

Kelly Syggelou

C

Christoph Aebi

V

Verena Wyss

M

Mariama Usman

E

Eric Giannoni

M

Martin Stocker

K

Klara M. Posfay-Barbe

U

Ulrich Heininger

S

Sara Bernhard-Stirnemann

A

Anita Niederer-Loher

C

Christian Kahlert

G

Giancarlo Natalucci

C

Christa Relly

T

Thomas Riedel

C

Christoph Berger

K

Katarina Vincek

T

Tina Plankar Srovin

N

Natalija Bahovec

P

Petra Prunk

V

Veronika Osterman

T

Tanja Avramoska

F

François Mallet

A

Alexandre Pachot

K

Kalifa Bojang

S

Syed M. A. Zaman

F

Fatou Secka

S

Suzanne Anderson

A

Anna Roca

I

Isatou Sarr

M

Momodou Saidykhan

S

Saffiatou Darboe

S

Samba Ceesay

U

Umberto D’Alessandro

C

Ching-Chuan Liu

S

Shih-Min Wang

R

Rachel P. J. Lai

G

Graeme Meintjes

Department of Medicine, University of Cape Town, Cape Town, South Africa

C

Christopher Chiu

M

Mauricio Barahona

Department of Mathematics, Imperial College London , London SW7 2AZ,

M

Myrsini Kaforou

A

Aubrey J. Cunnington