Sparse Coding Transcriptome Profiling Reduces Cost

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Solution Overview

Problem

High-cost and low-throughput of existing transcriptome-analysis technologies limit the widespread use of gene-expression profiling for applications such as disease classification and drug discovery, making it impractical to analyze thousands of compounds daily at a cost below conventional microarrays.

Innovation Solution

A cost-effective and flexible transcriptome-wide gene-expression profiling method using a probe set with 100 or more molecules, each with a tag linked to a probe for various transcripts, forming a Design Matrix, which allows for measuring relative abundances through sparse coding processes like non-negative matrix factorization and blind compressed sensing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional microarray technology is used for transcriptome analysis, then measurement precision is maintained, but cost increases and throughput decreases

Engineering Contradiction:

Improvegene expression measurement precisionVSAvoidthroughput of compound screening

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The transcriptome is segmented into a limited set of representative genes or gene modules that capture the essential biological variation. Instead of measuring all genes, the method segments the complex transcriptome into manageable components that can be measured efficiently with reduced reagent requirements, thereby increasing throughput while preserving measurement precision for the most informative genes.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention creates a universal probe set that can be applied across multiple applications including compound screening, disease classification, and biological mechanism exploration. This multi-functional probe set design allows the same platform to serve diverse research needs without requiring application-specific customization, thereby increasing overall productivity and reducing per-experiment cost.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Quantity of substance

If conventional microarray technology is used for transcriptome analysis, then comprehensive gene coverage is achieved, but cost increases

Engineering Contradiction:

Improvenumber of genes measuredVSAvoidcost of transcriptome analysis

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The method extracts and measures only the most informative genes or gene signatures that are sufficient for the intended application, rather than measuring the entire transcriptome. This extraction approach removes unnecessary measurement burden, reducing reagent consumption and manufacturing cost while maintaining the ability to achieve comprehensive biological insights through targeted gene selection.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention applies partial action by measuring a subset of genes that provides sufficient information for the research question at hand. Rather than performing excessive measurements of all genes, the method uses just enough measurements to achieve the desired biological understanding, thereby reducing cost while maintaining scientific rigor.

Inventive Principle:

Principle #16Partial or excessive action

3Measurement precision

If individual gene measurement is performed, then measurement precision is high, but throughput and cost efficiency decrease

Engineering Contradiction:

Improveindividual gene expression precisionVSAvoidrate of discovery

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The method merges information from multiple genes into composite gene signatures or modules that represent broader biological pathways or cellular states. By combining individual gene measurements into integrated signatures, the approach maintains the precision needed for biological interpretation while reducing the total number of measurements required, thereby increasing the rate of discovery through more efficient experimentation.

Inventive Principle:

Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach reduces the cost and increases throughput by enabling the inference of gene expression levels across the transcriptome with a small number of measurements, allowing for rapid discovery of medically relevant connections and identification of clinically effective therapies.

Implementation Method 1

contacting the probe library to the pool of samples

Methodology Applied

Scientific EffectHybridization: Absorption (physical)

Data Source

PatentUS11996168B2Systems and methods for determining relative abundances of biomolecules

Publication Date: 2024.05.28 THE BROAD INST INC

AI summary

The present invention relates to genomic informatics and gene-expression profiling. Gene-expression profiles provide complex molecular fingerprints regarding the relative state of a cell or tissue. Similarities in gene-expression profiles between organic states provide molecular taxonomies, classification, and diagnostics. Similarities in gene-expression profiles resulting from various external perturbations reveal functional similarities between these perturbagens, of value in pathway and mechanism-of-action elucidation. Similarities in gene-expression profiles between organic and induced states may identify clinically-effective therapies. Systems and methods herein provide for the measurement of relative gene abundances, including unbiased selection of and construction of probes and targets designed and methods for using known properties of sparsity of measurements to reach gene abundances.