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Serial RNA-seq of a single human

ABSTRACT: Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of human brain function over this timescale in healthy individuals are unknown. Over a period of 18 months, we performed intensive phenome-wide assessment of a single human, including brain connectivity using resting fMRI, measurements of psychological and physical health, and transcriptomic and metabolomic profiling. Brain connectivity varied across sessions in relation to behavioral variables including mood, fatigue, and food/caffeine intake, as well as variables related to inflammation and gut health. Pathway-based analysis of gene expression in peripheral lymphocytes identified associations with physical health and brain connectivity, including associations between specific brain networks and a broad set of immune-related pathways. Metabolomic measures were strongly associated with dietary variance. This study integrates dense neuroimaging and -omics profiling to provide a detailed picture of the joint dynamics of human brain and metabolic function over time, an approach that is critical for the understanding of brain disorders characterized by increased variability of brain function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE58122 | GEO | 2015/10/01

SECONDARY ACCESSION(S): PRJNA249059

REPOSITORIES: GEO

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Project description:The dynamics of human brain function are increasingly well understood at the short timescale of seconds/minutes (for example, through studies of learning) and the long timescale of years/decades (for example, through studies of development andageing), but almost nothing is known about how the human brainfunction varies across the range of days to months. This is a critical gap, because major psychiatric disorders show large fluctuations in brain function over this timescale. However, the kind of dense longitudinal phenotyping that is necessary to understand this question is extremely challenging with healthy human volunteers,who are unlikely to be sufficiently motivated to sustain frequent participation in a study over a long period. For this reason, the participation of motivated experimenters can be uniquely useful for demanding longitudinal studies. We investigated the long-range dynamics of brain function andtheir relation to a broad set of psychological and biological variables in a single healthy human (author R.A.P.) over the course of 532 days (along with several follow-up visits), representing one of the most intensive biological characterizations of a single individual ever performed (referred to hereafter as the MyConnectomestudy). The study was designed to measure the broadest possible range of human phenotypes (the phenome’3,4) to allow the widespread assessment of relations between psychological, neural and metabolic function. The results of the present study demonstrate that healthy brain function shows rich dynamics over the course of 18 months, and that these dynamics are paralleled by ongoing fluctuations in psychological and physiological function as observed in behaviour,gene expression and metabolomic measurements. These findings provide a proof of concept for the dynamic longitudinal phenotyping of individuals, which we propose will be crucial togain a better understanding of the substantial fluctuations in psychological and neural function in individuals with major psychiatric disorders.

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Serial RNA-seq of a single human

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