Plasma protein patterns as comprehensive indicators of health.
Stephen A WilliamsMika KivimakiClaudia LangenbergAroon D HingoraniJ P CasasClaude BouchardChristian JonassonMark A SarzynskiMartin J ShipleyLeigh AlexanderJessica AshTim BauerJessica ChadwickGargi DattaRobert Kirk DeLisleYolanda HagarMichael HinterbergRachel OstroffSophie WeissPeter GanzNicholas J WarehamPublished in: Nature medicine (2019)
Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.
Keyphrases
- public health
- healthcare
- mental health
- physical activity
- health information
- machine learning
- cardiovascular disease
- emergency department
- adipose tissue
- type diabetes
- alcohol consumption
- human health
- immune response
- dna methylation
- gene expression
- binding protein
- insulin resistance
- protein protein
- artificial intelligence
- body composition
- glycemic control
- depressive symptoms
- dendritic cells
- smoking cessation
- bone mineral density