An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Reports and Articles Social Processes and Proofs of Theorems and Programs

It is argued that formal verifications of programs, no matter how obtained, will not play the same key role in the development of computer science and software engineering as proofs do in mathematics. Furthermore the absence of continuity, the inevitability of change, and the complexity of specification of significantly many real programs make the formal verification process difficult to justify and manage. It is felt that ease of formal verification should not dominate program language design. Key Words and Phrases: formal mathematics, mathematical proofs, program verification, progra