Welcome to the SUBSPACE Consortium
The SUBtyping in SePsis And Critical illnEss (“SUBSPACE”) Consortium is a collaborative of leading researchers and clinicians to improve our understanding of sepsis and critical illness. Our goal is to further the understanding of subtyping (or ‘endotyping’) in critical illness by comparing and contrasting different existing subtype classifiers in several ways.
We believe that in patients with sepsis and other critical illnesses, a clear understanding of the immunological differences that are present will unlock a new way to find therapies that are tailored to each patient. We hope that this next era of personalized medicine in the ICU will lead to broadly improved outcomes.
BACKGROUND
The past decade has brought a huge growth in subtyping studies in sepsis and critical illness, most recently demonstrated by DeMerle, Angus and Seymour in their supplemental figure, copied here as Fig 1. Unfortunately, this has not been coupled with a flurry of new immune-modulating medicines for critical illness and sepsis.
Several review articles have covered both what subtypes exist, how they may further the practice of intensive care medicine, and how they should be classified and studied. Other work is underway arguing that subtypes may represent common ‘treatable traits’ across ostensibly separate critical syndromes. Indeed, recent work has confirmed in some cases the applicability of sepsis or ARDS subtypes in severe COVID-19; might this be the ‘tip of the iceberg’ in identifying pathophysiologic commonalities across critical illness?
A critical question is to what degree the various proposed classification systems overlap. Do subtyping schemas using clinical data, protein markers, and transcriptomes all tell us the same thing? Could there be multiple valid and overlapping ‘endotypes’ even within the same plane of information?
OUR VISION
What is needed is a common database that examines a broad representation of clinical illness, for which the different subtyping schemas are applied, such that they can be compared and contrasted with each other and across critical syndromes. A pooling of sepsis-3, sepsis-3 w/ shock, ARDS, severe COVID-19, trauma, burns, pancreatitis, non-infected critical medical patients, etc., would be ideal. But no single cohort with such characteristics exists that also has the necessary protein and transcriptomic samples / measurements. Thus, a multi-center effort to pool data across heterogeneous single retrospective cohorts may be the next best thing.
The follow-up analysis could then begin to answer several questions, such as:
How do various subtyping schemas continue to predict outcomes across various critical illnesses?
How do subtypes overlap across and within diagnoses?
Do multiple subtypes (e.g. a SENECA-delta & Calfee hyperinflammatory patient) lead to better predictions of outcomes or therapeutic response?
Are there any ‘universal’ subtypes in critical illness?
For inspiration, we might look to the oncology field: multiple (potentially overlapping) subtypes had been derived for colorectal cancer by 2013. An international consortium was able to run six of these subtyping methods in a very large pool of sample (N~4,000) to show that there were just four ‘consensus subtypes’ (Guinney, Nature Med, 2015). The paper has since been cited almost 2,500 times, and allowed the field to agree on the existence of a core group of subtypes of colorectal cancer, benefitting trialists and cancer biologists alike.
PRINCIPAL INVESTIGATORS
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TIM SWEENEY, MD, PhD
Principal Investigator
Co-Founder & CEO
Inflammatix -
ANGELA ROGERS, MD, MPH
Principal Investigator
Associate Professor of Medicine
Stanford Medicine -
PURVESH KHATRI, PhD
Principal Investigator
Associate Professor of Medicine
Stanford University
Co-Founder & Chief Scientist Inflammatix
SUBSPACE CONSORTIUM MEMBER SITES
Our member sites harbor our primary research staff who deal with the daily running of the technical aspects of SUBSPACE. These aspects include, but are not limited to: patient recruitment (in liaison with ICU research nurses and diagnostic laboratory staff); operation and troubleshooting of the diagnostic platforms under scrutiny; data acquisition; and entry into the SUBSPACE database.
Consortium membership is growing quickly - new sites are being added all the time!
Asst. Prof. Matthew Alder, Cincinnati Children’s Hospital Medical Center
Prof. Evangelos Giamarellos, National and Kapodistrian University of Athens and Hellenic Institute for the Study of Sepsis, Greece
Thomas Karvunidis, MD, PhD., Charles University, Teaching Hospital and Biomedical Center in Pilsen; Czech Republic
Prof. Ignacio Martin-Loeches, Trinity College Dublin, Ireland
Prof. Lyle Moldawer, University of Florida
Asst. Prof Nuala Meyer, University of Pennsylvania, USA
Prof. Tom van der Poll, Amsterdam UMC, Netherlands
BECOME A MEMBER
I want to join – what’s next?
We are interested in PIs who can contribute either clinical cohorts, or subtyping schema, or both. PIs would need to be willing to join roughly on the terms previously outlined and to submit de-identified clinical data formatted according to our final data dictionary standards.
In terms of clinical cohorts, a rough set of criteria is:
Sepsis or critical illness in acute phase (not recovery)
Day-of-admission encouraged (longitudinal data welcome)
Only clinical cohorts (no ex vivo, animal, etc)
Must have clinical data + at least transcriptomic / RNA-preserved blood samples, OR plasma / proteomic data. Other molecular data types are also welcome in addition
Strongly encouraged transcriptomic data or 2+ molecular data types
Healthy controls appreciated for molecular data
Missingness is tolerated and to be expected
CONTACT US
If you are interested and can contribute to either clinical cohorts, subtyping schema, or both, please reach out at info@subspace-study.net
SUBSPACE is currently funded and managed by Inflammatix, Inc.
