Systems and Methods for Determining Attributes of Biological Samples

• US 20190155987A1
• Filed: 05/02/2017
• Published: 05/23/2019
• Est. Priority Date: 05/02/2017
• Status: Active Grant

• Current Assignee: Liquid Biosciences, Inc.
• Original Assignee: Liquid Biosciences, Inc.
• Inventors: Lilley, Patrick, Walker, Beau
• Granted Patent: US 10,453,552 B2
• Time in Patent Office: Days
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 40/20 Supervised data analysis
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks

Abstract

Systems and methods of determining pre-quantitation attributes of biological samples using post-quantitation attributes of those samples is disclosed. By altering a set of biological samples in a measurable way before running the set through an instrument (e.g., a mass spectrometer), a model can be developed that enables determination of the unknown pre-quantitation attributes in other biological samples as a function of post-quantitation attributes.

Claims

1. A method of determining an unknown pre-quantitation attribute of a target biological sample using an electronic device, comprising the steps of:

receiving, via the electronic device, a set of biological data pairs, each biological data pair corresponding to a deliberately degraded biological sample and comprising a known pre-quantitation attribute and a set of post-quantitation attributes;

developing a model, via the electronic device using the set of biological data pairs, describing a relationship between (1) a subset of post-quantitation attributes and (2) the known pre-quantitation attribute; and

applying, via the electronic device, a set of target biological sample post-quantitation attributes to the model to determine the unknown pre-quantitation attribute of the target biological sample.

2. The method of claim 1, wherein the known pre-quantitation attribute comprises a type of deliberate degradation that the deliberately degraded biological sample has been subjected to.

3. The method of claim 2, wherein the known pre-quantitation attribute comprises at least one of exposure to heat, exposure to cold, exposure to ultraviolet light, exposure to chemical means, exposure to a denaturing reagent, exposure to an enzyme activity, exposure to radiation, exposure to agitation, exposure to pressure, and exposure to a change in pressure.

4. The method of claim 1, wherein the model comprises a plurality of models.

5. The method of claim 1, wherein the unknown pre-quantitation attribute comprises at least one of an indication of quality of the target biological sample.

6. The method of claim 1, wherein a post-quantitation attribute comprises an output of results from a mass spectrometer.

7. The method of claim 1, wherein the step of using the set of biological data pairs to computationally develop a model further comprises identifying and disregarding unnecessary post-quantitation attributes.

8. The method of claim 1, wherein the target biological sample comprises at least one of a blood sample, a protein serum sample, a tissue sample, a CSF sample, a urine sample, and a stool sample.

9. The method of claim 1, wherein a post-quantitation attribute of the set of post-quantitation attributes comprises at least one of a protein quantitation, a protein abundance, a protein concentration, a protein activity, a protein presence, a peptide quantitation, a peptide presence, a peptide abundance, an RNA activity, a wavelength emission measurement, a presence of post translational modifications, an amino acid sequence, and a mass to charge ratio value.

10. A method of determining a quality of a target biological sample using an electronic device, comprising the steps of:

receiving, via the electronic device, a set of biological data pairs, each biological data pair corresponding to a deliberately degraded biological sample and comprising a known quality and a set of post-quantitation attributes;

developing a model, via the electronic device using the set of biological data pairs, describing a relationship between (1) a subset of post-quantitation attributes and (2) the known quality;

applying, via the electronic device, a set of target biological sample post-quantitation attributes to the model to determine the quality of the target biological sample; and

wherein the model, via the electronic device, receives an input comprising the target biological sample post-quantitation attributes and produces an output comprising the quality of the target biological sample.

11. The method of claim 10, wherein the deliberately degraded biological sample is degraded such that the degradation corresponds to the known quality.

12. The method of claim 10, wherein the quality comprises a continuum ranging from low quality to high quality.

13. The method of claim 10, wherein the type of deliberate degradation comprises at least one of exposure to heat, exposure to cold, exposure to ultraviolet light, exposure to chemical means, exposure to a denaturing reagent, exposure to an enzyme activity, exposure to radiation, exposure to agitation, exposure to pressure, and exposure to a change in pressure.

14. The method of claim 10, wherein the target biological sample comprises at least one of a blood sample, a protein serum sample, a tissue sample, a CSF sample, a urine sample, and a stool sample.

15. The method of claim 10, wherein a post-quantitation attribute of the set of post-quantitation attributes comprises at least one of a protein quantitation, a protein abundance, a protein concentration, a protein activity, a protein presence, a peptide quantitation, a peptide presence, a peptide abundance, an RNA activity, a wavelength emission measurement, a presence of post translational modifications, an amino acid sequence, and a mass to charge ratio value.

16. The method of claim 10, wherein the model comprises a plurality of models.

17. A system for use with an instrument, where the system develops a model to determine an unknown pre-quantitation attribute of a target biological sample, comprising:

a computational modeling device communicatively coupled with the instrument, the instrument configured to analyze deliberately degraded biological samples to produce sets of post-quantitation attributes corresponding to the deliberately degraded biological samples;

wherein each deliberately degraded biological sample that has been analyzed by the instrument corresponds to a biological data pair, each biological data pair comprising a known pre-quantitation attribute and a set of post-quantitation attributes;

wherein the device;

receives sets of biological data pairs as input, and

computationally develops a model describing a relationship between (1) post-quantitation attributes and (2) the known pre-quantitation attribute, such that the model can be applied to a set of target biological sample post-quantitation attributes to determine the unknown pre-quantitation attribute of the target biological sample.

18. The system of claim 17, wherein the instrument is at least one of a mass spectrometer, a colorimeter, a spectrophotometer, a chromatograph, a gel electrophoresis system, a blood chemistry analyzer, a spectrofluorometer, an immunoassay system, proteomic assay systems, and an immunoturbidimetric system.

19. The method of claim 17, wherein the known pre-quantitation attribute comprises a type of deliberate degradation that the deliberately degraded biological sample has been subjected to.

20. The method of claim 17, wherein the type of deliberate degradation comprises at least one of exposure to heat, exposure to cold, exposure to ultraviolet light, exposure to chemical means, exposure to a denaturing reagent, exposure to an enzyme activity, exposure to radiation, exposure to agitation, exposure to pressure, and exposure to a change in pressure.

21. The method of claim 17, wherein the model comprises a plurality of models.