Databases 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 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 about 5 of said samples.
2 . The database of claim 1 further comprising numerical indices, said numerical indices obtained by mathematical computation of 2 said numerical values, said 2 numerical values corresponding to amounts of 2 nucleic acids in said number of samples wherein said numerical indices are directly comparable between 5 of said samples.
3 . The database as recited in claim 1 wherein said number is at least about 10 samples.
4 . The database as recited in claim 1 wherein 2 of said samples are obtained from different subjects.
5 . The database as recited in claim 1 wherein 2 of said samples are obtained at different times.
6 . The database as recited in claim 1 wherein said amounts show a coefficient of variation of less than about 25% between said 2 samples.
7 . The database as recited in claim 1 wherein at least one of said amounts is obtained using microfluidic capillary electrophoresis, oligonucleotide array, mass spectrometry, or chromatography.
8 . The database as recited in claim 1 wherein said amounts are not obtained using real-time measurements nor generation of a standard curve.
9 . The database as recited in claim 8 wherein said numerical indices are corrected for at least two sources of variation selected from cDNA loading, intra-nucleic acid amplification efficiency, inter-nucleic acid amplification efficiency, inter-specimen amplification efficiency, inter-sample amplification efficiency, and intra-sample amplification efficiency.
10 . The database as recited in claim 1 wherein said numerical values correspond to numbers of molecules of said 2 nucleic acids in said number of samples.
11 . The database as recited in claim 1 wherein at least one of said numerical indices indicates a biological state.
12 . The database as recited in claim 11 wherein said at least one numerical index is a balanced numerical index.
13 . The database as recited in claim 11 wherein said numerical index is calculated by dividing a numerator by a denominator, said numerator corresponding to said amount of one of said 2 nucleic acids and said denominator corresponding to said amount of the other of said 2 nucleic acids.
14 . The database as recited in claim 13 wherein said numerator corresponds to a gene positively associated with said biological state and said denominator corresponds to a gene negatively associated with said biological state.
15 . The database as recited in claim 11 wherein said biological state is a disease state, a predisposition to a disease state, a therapeutic drug response, a predisposition to a therapeutic drug response, an adverse drug response, a predisposition to an adverse drug response, is a drug toxicity, or a predisposition to a drug toxicity.
16 . The database as recited in claim 11 wherein said numerical indices are used in at least one stage of drug development selected from drug target screening, lead identification, pre-clinical validation, clinical trial and/or patient treatment.
17 . The database as recited in claim 1 wherein said nucleic acid comprises an RNA molecule.
18 . The database as recited in claim 1 wherein said nucleic acid comprises a DNA molecule.
19 . A method for obtaining a numerical index that indicates a biological state, comprising:
providing 2 samples corresponding to each of a first biological state and a second biological state;
assessing an amount of each of 2 nucleic acids in each of said 2 samples wherein said assessing can enumerate less than about 1,000 molecules of each of said 2 nucleic acids;
providing said amounts as numerical values wherein said numerical values are directly comparable between a number of samples;
mathematically computing said numerical values corresponding to each of said first and said second biological states; and
determining a mathematical computation that discriminates said first and said second biological states, thereby obtaining said numerical index.
20 . The method as recited in claim 19 wherein said determining said mathematic computation involves a use of software.
21 . The method as recited in claim 19 wherein said 2 nucleic acids are associated with said first biological state and not with said second biological state.
22 . The method as recited in claim 21 wherein one of said 2 nucleic acids is positively associated with said first biological state and the other of said 2 nucleic acids is negatively associated with said first biological state.
23 . The method as recited in claim 22 wherein said mathematical computation comprises dividing a numerator by a denominator, said numerator corresponding to said nucleic acid positively associated with said first biological state and said denominator corresponding to said nucleic acid negatively associated with said first biological state.
24 . The method as recited in claim 19 wherein said first biological state is a disease state and said second biological state is a non-disease state.
25 . The method as recited in claim 24 wherein said disease state is an angiogenesis-related condition, an antioxidant-related condition, an apotosis-related condition, a cardiovascular-related condition, a cell cycle-related condition, a cell structure-related condition, a cytokine-related condition, a defense response-related condition, a development-related condition, a diabetes-related condition, a differentiation-related condition, a DNA replication and/or repair-related condition, an endothelial cell-related condition, an folate receptor-related condition, an hormone receptor-related condition, an inflammation-related condition, an intermediary metabolism-related condition, a membrane transport-related condition, an oxidative metabolism-related condition, neurotransmission-related condition, a cancer-related condition, a protein maturation-related condition, a signal transduction-related condition, a stress response-related condition, a tissue structure-related condition, a transcription factor-related condition, a transport-related condition, or a xenobiotic metabolism-related condition.
26 . The method as recited in claim 1 wherein said direct comparison does not use a bioinformatics resource.
27 . A method comprising:
using a microarray to identify 2 nucleic acids associated with a first biological state and not with a second biological state;
providing 2 samples corresponding to each of said first biological state and said second biological state;
assessing an amount of each of said 2 nucleic acids in each of said 2 samples wherein said assessing can enumerate less than about 1,000 molecules of each of said 2 nucleic acids; and
mathematically computing said amounts corresponding to each of said first and said second biological states to determine a numerical index, said numerical index discriminating said first and said second biological states.
28 . The method as recited in claim 26 wherein said mathematical computation involves a use of software.
29 . The method as recited in claim 27 wherein said software comprises a machine learning software.
30 . The method as recited in claim 26 wherein one of said 2 nucleic acids is positively associated with said first biological state and the other of said 2 nucleic acids is negatively associated with said first biological state.
31 . The method as recited in claim 29 wherein said mathematical computation comprises dividing a numerator by a denominator, said numerator corresponding to said nucleic acid positively associated with said first biological state and said denominator corresponding to said nucleic acid negatively associated with said first biological state.
32 . A method of identifying a biological state comprising:
assessing an amount each of 2 nucleic acids in a first sample, wherein said assessing can enumerate less than about 1,000 molecules of each of said 2 nucleic acids in said first sample;
providing said amounts as numerical values wherein said numerical values are directly comparable between a number of samples; and
using said numerical values to provide a numerical index, whereby said numerical index indicates said biological state.
33 . A method of identifying a biological state comprising:
assessing an amount a nucleic acid in a first sample, wherein said assessing can enumerate less than about 1,000 molecules of said nucleic acid in said first sample; and
providing said amount as a numerical value wherein said numerical value is directly comparable between a number of other samples.
34 . The method as recited in claim 32 wherein said biological state corresponds to a normal expression level of a first gene.