Business methods for assessing nucleic acids
The present invention is directed to methods and compositions for evaluating nucleic acids, methods of preparing such compositions, and applications and business methods employing such compositions and methods. In particular, the present invention provides business methods for operating a gene expression measurement service.
1 . A business method comprising:
collecting a first specimen comprising a first nucleic acid;
measuring an amount of said first nucleic acid in a first sample of said first specimen wherein said measuring can enumerate less than about 1,000 molecules of said first nucleic acid in said first sample; and
providing said amount as a numerical value wherein said numerical value allows direct comparison to an amount of said first nucleic acid in a second sample.
2 . The method as recited in claim 1 wherein said first and said second samples are measured at different times.
3 . The method as recited in claim 1 wherein said first and said second samples are collected from different subjects.
4 . The method as recited in claim 1 wherein said measurement provides a coefficient of variation of less than about 50% for said first nucleic acid.
5 . The method as recited in claim 1 wherein said measuring step is performed at least about 100 times per day.
6 . The method as recited in claim 1 wherein said first nucleic acid comprises an RNA molecule.
7 . The method as recited in claim 1 wherein said first nucleic acid comprises a DNA molecule.
8 . The method as recited in claim 1 wherein said method comprises an automated step.
9 . The method as recited in claim 1 wherein said method comprises a use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or chromatography.
10 . The method as recited in claim 1 wherein said first specimen comprises at least about 1,000 cells.
11 . The method as recited in claim 1 wherein said first specimen comprises a human specimen.
12 . The method as recited in claim 11 wherein said human specimen is collected without identifying information.
13 . The method as recited in claim 11 , further comprising collecting information attesting to compliance with investigative protocol.
14 . The method as recited in claim 13 wherein said identifying information is collected at a later time than said collection of said first specimen.
15 . The method as recited in claim 1 , further comprising collecting information selecting a number of nucleic acids in said first specimen to be assessed.
16 . The method as recited in claim 15 wherein said information is collected via a website.
17 . The method as recited in claim 16 , further comprising identifying which of said selected nucleic acids electrophoresis together.
18 . The method as recited in claim 17 wherein amounts of said identified nucleic acids are electrophoresed simultaneously.
19 . The method as recited in claim 1 wherein said numerical value is provided via e-mail.
20 . The method as recited in claim 1 wherein said assessing comprises:
providing a standardized mixture comprising a competitive template for said first nucleic acid and a competitive template for a second nucleic acid in said first specimen wherein said competitive templates are at known concentrations relative to each other;
combining said standardized mixture with a first sample of said specimen, co-amplifying said first nucleic acid and said competitive template for said first nucleic acid to produce fist amplified product thereof;
diluting said first amplified product;
further co-amplifying said diluted first amplified product of said first nucleic acid and of said competitive template for said first nucleic acid, to produce second amplified product thereof; and
co-amplifying said second nucleic and said competitive template for said second nucleic acid to produce first amplified product thereof.
21 . The method as recited in claim 20 , further comprising:
obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid and said second amplified product of said competitive template for said first nucleic acid;
obtaining a second relationship, said second relationship comparing said first amplified product of said second nucleic acid and said first amplified product of said competitive template for said second nucleic acid; and
comparing said first and said second relationships.
22 . The method as recited in claim 21 wherein said second nucleic acid serves as a reference nucleic acid.
23 . The method as recited in claim 22 wherein said standardized mixture further comprises sufficient amounts of said competitive templates for assessing said first nucleic acid in more than about 106 samples.
24 . A business method of improving drug development, comprising:
collecting a first specimen comprising a nucleic acid from a first biological entity administered a candidate drug at first stage of drug development;
collecting a second specimen comprising said nucleic acid from a second biological entity at a second stage of drug development;
assessing an amount of said nucleic acid in each of said first and said second specimen;
directly comparing said amounts; and
altering a step of said drug development based on said comparison.
25 . The method as recited in claim 24 wherein said first or said second biological entity is at least one entity selected from a virus, a cell, a tissue; an in vitro culture, a plant, an animal, and a subject participating in a clinical trial.
26 . The method as recited in claim 24 wherein said first or said second stage of drug development comprises at least 2 stages selected from drug target screening, lead identification, pre-clinical validation, clinical trial and patient treatment.
27 . The method as recited in claim 26 wherein said pre-clinical validation comprises a bioassay and/or an animal study.
28 . The method as recited in claim 1 wherein said altering comprises a stratification of a clinical trial.
29 . The method as recited in claim 28 wherein said stratification involves identifying subjects to have a reduced side effect.
30 . The method as recited in claim 1 wherein said altering reduces the time for said drug development.
31 . A business method of improving drug development, comprising:
providing a database comprising numerical values corresponding to amounts of a first nucleic acid in a number of samples wherein said numerical values are directly comparable between 5 of said samples;
collecting a first specimen comprising said first nucleic acid from a biological entity administered a candidate drug at a stage of drug development;
assessing an amount of said first nucleic acid in a first sample of said first specimen;
directly comparing said amount to at least one of said numerical values in said database; and
altering a step of said drug development based on said comparison.
32 . The method as recited in claim 31 wherein said biological entity is at least one entity selected from a virus, a cell, a tissue, an in vitro culture, a plant, an animal, and a subject participating in a clinical trial.
33 . The method as recited in claim 31 wherein said stage of drug development comprises at least one stage selected from drug target screening, lead identification, pre-clinical validation, clinical trial and patient treatment.
34 . The method as recited in claim 33 wherein said pre-clinical validation comprises a bioassay and/or an animal study.
35 . The method as recited in claim 31 wherein said altering comprises a stratification of a clinical trial.
36 . The method as recited in claim 35 wherein said stratification involves identifying subjects to have a reduced side effect.
37 . The method as recited in claim 31 wherein said altering reduces the time for said drug development.
38 . A business method of improving drug development, comprising:
providing a database comprising numerical indices, said numerical indices obtained by mathematical computation of 2 numerical values corresponding to amounts of 2 nucleic acids in a number of samples wherein said numerical indices are directly comparable between 5 of said samples;
collecting a first specimen comprising said 2 nucleic acids from a biological entity administered a candidate drug at a stage of drug development;
assessing an amount of each of said 2 nucleic acids in a first sample of said first specimen;
using said 2 amounts to mathematically compute a first numerical index;
directly comparing said first numerical index to at least one of said numerical indices in said database; and
altering a step of said drug development based on said comparison.
39 . The method as recited in claim 38 wherein said biological entity is at least one entity selected from a virus, a cell, a tissue, an in vitro culture, a plant, an animal, and a subject participating in a clinical trial.
40 . The method as recited in claim 38 wherein said stage of drug development comprises at least one stage selected from drug target screening, lead identification, pre-clinical validation, clinical trial and patient treatment.
41 . The method as recited in claim 40 wherein said pre-clinical validation comprises a bioassay and/or an animal study.
42 . The method as recited in claim 38 wherein said altering comprises a stratification of a clinical trial.
43 . The method as recited in claim 42 wherein said stratification involves identifying subjects to have a reduced side effect.
44 . The method as recited in claim 38 wherein said altering reduces the time for said drug development.