Circadian Time Estimation Using 18-Gene Biomarker Panel
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Solution Overview
Problem
Current methods for assessing human circadian rhythms are invasive, costly, and lack generalizability across different studies and platforms, requiring serial sampling over extended periods and failing to accurately predict circadian time from a minimal number of samples.
Innovation Solution
A method using a panel of biomarkers, including CLEC10A, PER1, GHRL, IL1B, NR1D1, DDIT4, GNG2, LLGL2, NR1D2, CD1C, DHRS13, GPCPD1, TIAM2, CD38, GZMB, ZNF438, and PDK1, detected through microarray or RNA-Seq, with a within-subject normalization procedure and periodic elastic net predictor to accurately estimate circadian time from two blood samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If serial sampling over extended periods is used to assess circadian rhythms, then measurement accuracy is improved, but loss of time and productivity deteriorate
Solution Approach 1:
The patent extracts the essential circadian rhythm information into a compact biomarker panel of 18 genes that can be measured in just two blood samples spaced 4+ hours apart. This extracted biomarker signature captures the core temporal information without requiring extended serial sampling, thereby resolving the contradiction between measurement accuracy and time loss.
Solution Approach 2:
The patent transforms the measurement approach by changing from continuous serial sampling to discrete two-timepoint sampling with a specific 4+ hour interval. This parameter change in sampling frequency and timing, combined with the biomarker panel, maintains circadian time estimation accuracy while dramatically reducing the total assessment time required.
2Measurement precision
If multiple blood samples are collected for circadian assessment, then measurement precision is improved, but object-generated harmful factors worsen due to increased invasiveness
Solution Approach 1:
The patent extracts circadian rhythm information from just two blood samples using an 18-gene biomarker panel, minimizing the invasive sampling requirement while maintaining measurement precision. This extraction approach reduces the harmful effects of repeated blood collection compared to traditional serial sampling methods.
Solution Approach 2:
The patent uses exactly two blood samples spaced 4+ hours apart, which is the minimum sufficient action to capture circadian phase information accurately. This partial sampling approach (rather than extensive serial sampling) reduces invasiveness while maintaining the necessary measurement precision for circadian assessment.
3Measurement precision
If study-specific normalization procedures are used, then measurement precision within a single study is improved, but adaptability across different studies and platforms deteriorates
Solution Approach 1:
The patent develops a universal normalization procedure that works across multiple studies and platforms (microarray, RNA-Seq) without requiring study-specific calibration. This universal approach, combined with the 18-gene biomarker panel, enables the same analytical pipeline to accurately estimate circadian time across diverse datasets, resolving the contradiction between within-study precision and cross-study adaptability.
Solution Approach 2:
The patent applies normalization and filtering procedures preliminarily to the biomarker expression data before circadian time estimation. This preliminary processing step standardizes the data from different studies and platforms, enabling subsequent accurate analysis without requiring study-specific adjustments, thereby achieving both precision and generalizability.
Data Source
AI summary
Provided herein are biomarkers of endogenous biological time (e.g. circadian time). In particular compositions and methods are provided for assessing the biological time of a subject, and diagnosis of diseases/conditions and/or providing treatments based thereon.