Bioinformatic Detection of Rare GAM Oligonucleotides
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Solution Overview
Problem
Current methods for detecting microRNA oligonucleotides are limited in sensitivity, failing to detect rare or low-abundance miRNA species that do not present a visible phenotype or produce sufficient RNA for standard molecular biology techniques, leading to an underestimation of their number and role in human biology.
Innovation Solution
The discovery of 122,764 novel human regulatory microRNA-like oligonucleotides, referred to as Genomic Address Messenger (GAM) oligonucleotides, which are detectable using a novel bioinformatic approach and can inhibit translation by hybridizing to untranslated regions of target genes, along with 18,602 microRNA-cluster like polynucleotides, known as Genomic Record (GR) polynucleotides, enabling the modulation of gene expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If standard molecular biological techniques are used to detect microRNA oligonucleotides, then commonly abundant miRNA species can be detected, but rare or low-abundance miRNA species that do not present a visible phenotype or produce sufficient RNA cannot be detected
Solution Approach 1:
The patent employs bioinformatic copying and simulation of miRNA detection processes using computational models. Virtual miRNA sequences are generated and analyzed through in silico cloning and sequencing simulations, allowing detection of rare miRNA species without requiring physical isolation or standard molecular biology techniques. This computational copying enables sensitivity enhancement for low-abundance targets.
Solution Approach 2:
The patent replaces mechanical laboratory techniques (cloning, sequencing, Northern blots) with computational algorithms and bioinformatic analysis. By substituting physical detection methods with computer-based simulation and data processing, the system achieves enhanced sensitivity for detecting rare miRNA species that would be invisible to conventional experimental approaches.
2Productivity
If conventional cloning and sequencing methods are used, then prevalent miRNA oligonucleotides can be identified, but rare miRNA oligonucleotides representing less than 1% of all small RNA segments remain undetected
Solution Approach 1:
The patent performs preliminary bioinformatic prediction and identification of miRNA sequences before experimental verification. By pre-screening computational models and virtual libraries, the system identifies candidate rare miRNA species that can then be targeted for selective detection, significantly increasing the number of detectable species beyond what conventional random sampling methods allow.
Solution Approach 2:
The patent transitions from two-dimensional experimental detection (limited by RNA quantity and visible phenotype) to three-dimensional computational analysis incorporating sequence structure, evolutionary conservation, and predictive algorithms. This dimensional expansion enables detection of rare miRNA species based on multiple computational criteria rather than solely on abundance or phenotypic visibility.
3Loss of information
If limited number of clones are sequenced, then commonly abundant miRNA can be discovered, but the total number of miRNA oligonucleotides in the genome is severely underestimated
Solution Approach 1:
The patent employs self-service computational algorithms that automatically predict, identify, and characterize miRNA sequences without requiring extensive manual analysis. The bioinformatic system performs self-contained analysis of sequence structures, folding patterns, and target predictions, enabling comprehensive detection of rare miRNA species through automated processing rather than labor-intensive experimental verification.
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 allows for the detection and modulation of previously undetectable miRNA oligonucleotides, revealing their significant role in regulating thousands of proteins and their association with major diseases, challenging the long-held belief in the insignificance of non-protein-coding regions of the genome and providing a new understanding of cell differentiation and disease mechanisms.
Implementation Method 1
Each GAM oligonucleotide specifically inhibits translation of one of more target genes by hybridization of an RNA transcript encoded by the GAM, to a site located in an untranslated region (UTR) of the mRNA of one or more of the target genes
Data Source
AI summary
The present invention describes a novel approach whereby small molecules may be used to modulate activity of microRNA and GAM oligonucleotides. This mode of therapy allows inter alia up regulation of a disease-related target gene of novel GAM oligonucleotides of the present invention, by countering the activity of a GAM oligonucleotides which naturally inhibits expression of that target gene. Nucleic acid molecules are provided respectively encoding 122,764 GAM oligonucleotides and their respective precursors, and 18602 GR polynucleotides, as are vectors and probes both comprising the nucleic acid molecules, and methods and systems for detecting GAM oligonucleotides and GR polynucleotides and specific functions and utilities thereof, for detecting expression of GAM oligonucleotides and GR polynucleotides, and for selectively enhancing and selectively inhibiting translation of the respective target genes thereof.