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Databases for assessing nucleic acidsRelated Patent Categories: Data Processing: Measuring, Calibrating, Or Testing, Measurement System In A Specific Environment, Biological Or Biochemical, Gene Sequence DeterminationDatabases for assessing nucleic acids description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060190192, Databases for assessing nucleic acids. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE [0001] This application claims the benefit of U.S. Provisional Application No. 60/646,157, filed Jan. 21, 2005, which is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION [0003] With the sequencing of the human genome comes the hope of accelerating drug development and discovering better diagnostic tests. This hope has engendered a need to develop improved methods for multi-gene expression measurement. Methods amenable to appropriate quality control, for example, to meet regulatory guidelines, are particularly needed. The present invention relates to compositions and methods directed to addressing these hopes and needs. [0004] Other methods and compositions directed thereto are provided in U.S. patent application Ser. No. 10/109,349, filed Mar. 28, 2002, and Ser. No. 10/471,473; and U.S. Provisional Application Ser. Nos. 60/368,288 and 60/368,409, filed Mar. 28, 2002; 60/550,278, filed Mar. 5, 2004 and 60/561,841, filed Apr. 12, 2004. SUMMARY OF THE INVENTION [0005] A first aspect of the invention is a method comprising providing a first sample comprising a first nucleic acid; amplifying said first nucleic acid; and obtaining a relationship wherein said relationship can enumerate less than about 1,000 molecules of said first nucleic acid in said first sample. In some embodiments of the invention said relationship can enumerate less than about 100 molecules, less than about 10 molecules, or less than about 1 molecule of said first nucleic acid in said first sample. In other embodiments, said relationship compares a first relationship of amplified product of said first nucleic acid to co-amplified product of a competitive template for said first nucleic acid to a second relationship of amplified product of a second nucleic acid in said first sample to co-amplified product of a competitive template for said second nucleic acid. Typically, the said first nucleic acid and said competitive template for said first nucleic acid are co-amplified in a first vessel and said second nucleic acid and said competitive template for said second nucleic acid are co-amplified in a second vessel. The competitive template for the first or second nucleic acid can comprise a sequence referenced in Table 4. In some embodiments, the second nucleic acid serves as a first reference nucleic acid, for example as a control for loading. The first reference nucleic acid can correspond to at least one gene selected from GADP, ACTB, and .beta.-actin. The relationship can further compare amplified product of a number of other nucleic acid(s) to co-amplified product of competitive template(s) for said number of other nucleic acid(s). At least one of said other nucleic acids can serve as a second reference nucleic acid. The second reference nucleic acid can correspond to at least one gene selected from GADP, ACTB, and .beta.-actin. In various embodiments, the relationship comprises a use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or a chromatography. In some embodiments, the relationship does not involve taking real-time measurements nor generation of a standard curve. The relationship can control for 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. The relationship is capable of detecting less than about a two-fold difference or less than about a one-fold difference. The relationship is capable of detecting less than about an 80% difference, less than about a 50% difference, less than about a 30% difference, or less than about a 20% difference. In some embodiments, the relationship is capable of detecting less than about a two-fold difference or less than about a one-fold difference in about 100 molecules or less or in about 10 molecules or less of said first nucleic acid in said first sample. The difference detected can be less than about an 80% difference, less than about a 50% difference, less than about a 30% difference, or less than about a 20% difference. In some embodiments, the relationship provides a coefficient of variation of less than about 25%, less than about 20%, less than about 15%, less than about 10%, or less than about 5% between said first sample and a second sample of said first nucleic acid. In some embodiments, the first and said second samples are amplified at different times, first and said second samples are amplified in different laboratories, or the first and said second samples are provided from different subjects. The first nucleic acid can comprise a sequence referenced in Table 1 or 2. The methods described herein can reduce or eliminate the false negatives; preferably the false positives are reduced to a statistically insignificant number. The nucleic acid can be an RNA molecule or a DNA molecule. Typically, the relationship is substantially constant beyond an exponential phase of said amplification of said first nucleic acid. [0006] Another embodiment is a method of assessing a first nucleic acid provided in a first sample, comprising co-amplifying said first nucleic acid, a number of other nucleic acid(s), a competitive template for said first nucleic acid and a competitive template(s) for said other nucleic acid(s) wherein said competitive templates are at known concentrations relative to one another, to produce first amplified product thereof; diluting said first amplified product; and 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. Typically, the number is at least about one other nucleic acid, at least about 100 other nucleic acids, or the number is at least about 1,000 other nucleic acids. Typically, the diluting produces at least about a 100-fold dilution, at least about a 1,000-fold dilution, or at least about a 10,000-fold dilution. Preferably, the method enumerates less than about 1,000 molecules of said first nucleic acid in said sample, less than about 100 .mu.molecules of said first nucleic acid in said first sample, less than about 10 molecules of said first nucleic acid in said first sample, or about 1 molecule of said first nucleic acid in said first sample. Preferably, at least one of said competitive templates comprises a sequence referenced in Table 4. The first nucleic acid can comprise a sequence referenced in Table 1 or 2. One of the other nucleic acids can serve as a first reference nucleic acid, such as a control for loading. The first reference nucleic acid can correspond to at least one gene selected from GADP, ACTB, and .beta.-actin. In one embodiment, the method of assessing comprises obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid to 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 first reference nucleic acid to said first amplified product of said competitive template for said first reference nucleic acid; and comparing said first and said second relationships. In some embodiments, another one of said other nucleic acids serves as a second reference nucleic acid. The second reference nucleic acid can corresponds to at least one gene selected from GADP, ACTB, and .beta.-actin. In another embodiment, the method of assessing comprises obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid to said second amplified product of said competitive template for said first nucleic acid; obtaining a third relationship, said third relationship comparing said first amplified product of said second reference nucleic acid to said first amplified product of said competitive template for said second reference nucleic acid; and comparing said first and said third relationships. In some embodiments, the method further comprises diluting and further co-amplifying said diluted first amplified product of said first reference nucleic acid and of said competitive template for said first reference nucleic acid, to produce second amplified products thereof. In yet anotehr embodiment, the assessing comprises obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid to said second amplified product of said competitive template for said first nucleic acid; obtaining a fourth relationship, said fourth relationship comparing said second amplified product of said first reference nucleic acid to said second amplified product of said competitive template for said first reference nucleic acid; and comparing said first and said fourth relationships. In various embodiments, the relationship comprises a use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or a chromatography. In some embodiments, the relationship does not involve taking neither real-time measurements nor generation of a standard curve. The relationship can control for 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. The assessing can detect less than about a two-fold difference, less than about a one-fold difference, less than about an 80% difference, less than about a 50% difference, less than about a 30% difference, or less than about a 20% difference. In some embodiments, the relationship provides a coefficient of variation of less than about 25%, less than about 20%, less than about 15%, less than about 10%, or less than about 5% between said first sample and a second sample of said first nucleic acid. In some embodiments, the first and said second samples are amplified at different times, first and said second samples are amplified in different laboratories, or the first and said second samples are provided from different subjects. The first nucleic acid can comprise a sequence referenced in Table 1 or 2. The methods described herein can reduce or eliminate the false negatives; preferably the false positives are reduced to a statistically insignificant number. The nucleic acid can be an RNA molecule or a DNA molecule. Typically, the relationship is substantially constant beyond an exponential phase of said amplification of said first nucleic acid. In some embodiments, the samples are diluted prior to amplification. [0007] Another aspect of the invention is a method of assessing a first nucleic acid in a first sample, comprising 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 sample wherein said competitive templates are at known concentrations relative to each other; combining said first sample with said standardized mixture; co-amplifying said first nucleic acid and said competitive template for said first nucleic acid to produce first 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 acid and said competitive template for said second nucleic acid to produce first amplified product thereof. The first nucleic acid and said competitive template for said first nucleic acid can be co-amplified in a first vessel and said second nucleic acid and said competitive template for said second nucleic acid can be co-amplified in a second vessel. Typically, the diluting produces at least about a 100-fold dilution, at least about a 1,000-fold dilution, or at least about a 10,000-fold dilution. The method can enumerate less than about 1,000 molecules of said first nucleic acid in said first sample, less than about 100 molecules of said first nucleic acid in said first sample, less than about 10 molecules of said first nucleic acid in said first sample, or about 1 molecule of said first nucleic acid in said first sample. The standardized mixture can further comprise sufficient amounts of said competitive templates for assessing said first nucleic acid in more than about 10.sup.6 other samples, more than about 10.sup.8 other samples, more than about 10.sup.10 other samples, more than about 10.sup.11 other samples, or more than about 10.sup.12 other samples. The standardized mixture can further comprise a number of other competitive template(s) for other nucleic acid(s) wherein said competitive template(s) are at known concentrations relative to one another; thereby allowing assessment of said other nucleic acids in said first sample. The number of other competitive templates can be at least about 100 or at least about 1,000. In some embodiments, the second nucleic acid serves as a first reference nucleic acid, such as a control for loading. The first reference nucleic acid can correspond to at least one gene selected from GADP, ACTB, and .beta.-actin. In some embodiments, the method of assessing comprises obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid to 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 first reference nucleic acid to said first amplified product of said competitive template for said first reference nucleic acid; and comparing said first and said second relationships. At least one of said other nucleic acids serves as a second reference nucleic acid and said second reference nucleic acid can correspond to at least one gene selected from GADP, ACTB, and .beta.-actin. The method can further comprise co-amplifying said second reference nucleic acid and said competitive template for said second reference nucleic acid to produce first amplified product thereof. The assessing can comprise obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid to said second amplified product of said competitive template for said first nucleic acid; obtaining a third relationship, said third relationship comparing said first amplified product of said second reference nucleic acid to said first amplified product of said competitive template for said second reference nucleic acid; and comparing said first and said third relationships. The standardized mixture can further comprise sufficient amounts of said competitive templates for assessing said first nucleic acid in more than about 10.sup.6 other samples, more than about 10.sup.8 other samples, more than about 10.sup.10 other samples, more than about 10.sup.11 other samples, or more than about 10.sup.12 other samples. The method can further comprise diluting and further co-amplifying said diluted first amplified product of said first reference nucleic acid and of said competitive template for said first reference nucleic acid, to produce second amplified products thereof. In one embodiment, the first nucleic acid and said competitive template for said first nucleic acid are further co-amplified in a first vessel and said first reference nucleic acid and said competitive template for said first reference nucleic acid are further co-amplified in a second vessel. In another embodiment, the assessing comprises obtaining a first relationship, said first relationship comparing said second amplified product of said first nucleic acid to said second amplified product of said competitive template for said first nucleic acid; obtaining a fourth relationship, said fourth relationship comparing said second amplified product of said first reference nucleic acid to said second amplified product of said competitive template for said first reference nucleic acid; and comparing said first and said fourth relationships. In various embodiments, the relationship comprises a use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or a chromatography. In some embodiments, the relationship does not involve taking neither real-time measurements nor generation of a standard curve. The relationship can control for 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. The assessing can detect less than about a two-fold difference, less than about a one-fold difference, less than about an 80% difference, less than about a 50% difference, less than about a 30% difference, or less than about a 20% difference. In some embodiments, the relationship provides a coefficient of variation of less than about 25%, less than about 20%, less than about 15%, less than about 10%, or less than about 5% between said first sample and a second sample of said first nucleic acid. In some embodiments, the first and said second samples are amplified at different times, first and said second samples are amplified in different laboratories, or the first and said second samples are provided from different subjects. The first nucleic acid can comprise a sequence referenced in Table 1 or 2. The methods described herein can reduce or eliminate the false negatives, preferably the false positives are reduced to a statistically insignificant number. The nucleic acid can be an RNA molecule or a DNA molecule. [0008] Another aspect of the invention is a method for assessing a first nucleic acid, comprising providing a series of serially-diluted standardized mixtures comprising a competitive template for said first nucleic acid and a competitive template for a second nucleic acid present in a number of samples comprising said first nucleic acid, wherein said competitive templates are at known concentrations relative to each other; combining one of said samples comprising said first nucleic acid with a first one of said serially-diluted standardized mixtures; co-amplifying said first nucleic acid and said competitive template for said first nucleic acid to produce amplified product thereof; obtaining a first relationship, said first relationship comparing said amplified product of said first nucleic acid to said amplified product of said competitive template for said first nucleic acid; determining whether said first relationship is within about 1:10 to about 10:1; if not, repeating said combining, co-amplifying, obtaining and determining steps with a second one of said serially-diluted standardized mixtures; co-amplifying said second nucleic acid and said competitive template for said second nucleic acid to produce amplified product thereof; obtaining a second relationship, said second relationship comparing said amplified product of said second nucleic acid to said amplified product of said competitive template for said second nucleic acid; and comparing said first and said second relationships. The method can further comprise diluting said amplified product of said first nucleic acid and said competitive template for said first nucleic acid; and further co-amplifying said diluted amplified product to produce further amplified product thereof. In addition, the method can further comprise diluting said amplified product of said second nucleic acid and said competitive template for said second nucleic acid; and further co-amplifying said diluted amplified product to produce further amplified product thereof. The number of samples can comprise a series of serially-diluted samples of said second nucleic acid. In one embodiment of the one of said samples is selected to provide said second nucleic acid approximately calibrated to said competitive template for said second nucleic acid in said first one of said serially-diluted standardized mixtures. In another embodiment of the method said first nuclei acid and said competitive template for said first nucleic acid are co-amplified in a first vessel and said second nucleic acid and said competitive template for said second nucleic acid are co-amplified in a second vessel. The second nucleic acid can serve as a first reference nucleic acid, such as a control for loading. The first reference nucleic acid can be GADP, ACTB, or .beta.-actin. The first reference nucleic acid can be present at two different concentrations in two of said serially-diluted standardized mixtures. The series of serially-diluted standardized mixtures can further comprise sufficient amounts of said competitive templates for assessing said first nucleic acid in more than about 10.sup.6 samples, more than about 10.sup.8 samples, more than about 10.sup.10 samples, more than about 10.sup.11 samples, or more than about 10.sup.12 samples. The series of serially-diluted standardized mixtures can further comprise a number of other competitive template(s) for other nucleic acid(s) wherein said competitive template(s) are at known concentrations relative to one another, thereby allowing assessment of said other nucleic acid(s). This number can be at least about 100 other competitive templates or at least about 1,000 other competitive templates. The at least one of said other nucleic acids can serve as a second reference nucleic acid. The second reference nucleic acid can correspond to at least one gene selected from GADP, ACTB, and .beta.-actin. The method of assessing can further comprise co-amplifying said second reference nucleic acid and said competitive template for said second reference nucleic acid to produce amplified product thereof; obtaining a third relationship, said third relationship comparing said amplified product of said second reference nucleic acid to said amplified product of said competitive template for said second reference nucleic acid; and comparing said first and said third relationships. The series of serially-diluted standardized mixtures can further comprise sufficient amounts of said number of other competitive template(s) for assessing said other nucleic acid(s) in more than about 10.sup.6 samples, in more than about 10.sup.8 samples, or in more than about 10.sup.10 samples. The series of serially-diluted standardized mixtures can further comprise sufficient amounts of said number of other competitive template(s) for assessing said other nucleic acid(s). The series of serially-diluted standardized mixtures can further comprise sufficient amounts of said number of other competitive template(s) for assessing said other nucleic acid(s) in more than about 10.sup.11 samples or in more than about 10.sup.12 samples. The method can be performed such that said first nucleic acid and said other nucleic acid(s) vary in amount over a range of more than about 2 orders of magnitude. The method can detect less than about a two-fold difference over said range, less than about a 50% difference over said range, or less than about a 20% difference over said range. In some embodiments of the method, said first nucleic acid and said other nucleic acid(s) vary in amount over a range of about 3 or more orders of magnitude and said assessing detects less than about a two-fold difference over said range, less than about a 50% difference over said range, or less than about a 20% difference over said range. In other embodiments of the method, the first nucleic acid and said other nucleic(s) vary in amount over a range of about 4 or more orders of magnitude and the assessing detects less than about a two-fold difference over said range, less than about a 50% difference over said range or less than about a 20% difference over said range. In some embodiments, the first nucleic acid and said other nucleic acid(s) vary in amount over a range of about 6 or more orders of magnitude and the assessing detects less than about a two-fold difference over said range, less than about a one-fold difference over said range, less than about an 80% difference over said range, less than about a 50% difference over said range, less than about a 30% difference over said range, or less than about a 20% difference over said range. In some methods, the first nucleic acid and said other nucleic acid(s) vary in amount over a range of about 7 or more orders of magnitude and said enumerating detects less than about a two-fold difference over said range, detects less than about a one-fold difference over said range, less than about an 80% difference, less than about a 50% difference, or less than about a 20% difference. The range can also be about 8, about 9, about 10, or about 15. In some methods the about 7 orders of magnitude span about a 7-log range of gene expression and said about 7 orders of magnitude can include about 10.sup.-3, about 10.sup.-2, about 0.1, about 1, about 10, about 10.sup.2, about 10.sup.3, and about 10.sup.4 copies/cell. The first nucleic acid can comprise a sequence referenced in Table 1 or 2. The competitive template for said first or said second nucleic acid can comprise a sequence referenced in Table 4. The competitive template for said first nucleic acid can be at a series of concentrations relative to said competitive template for said second nucleic acid. The series of concentrations can provide 10-fold serial dilutions of said competitive template for said first nucleic acid relative to said competitive template for said second nucleic acid. At least two of said series of concentrations can span about one order of magnitude, at least two of said series of concentrations span about three orders of magnitude, or at least two of said series of concentrations span about 6 orders of magnitude. The series of concentrations can include at least two concentrations selected from about 10.sup.-11 M, about 10.sup.-12 M, about 10.sup.-13 M, about 10.sup.-14 M, about 10.sup.-15 M, and about 10.sup.-16 M. The series of concentrations can include at least three concentrations selected from about 10.sup.-11 M, about 10.sup.-12 M, about 10.sup.-13 M, about 10.sup.-14 M, about 10.sup.-15 M, and about 10.sup.-16 M. The series of concentrations can include at least six concentrations of about 10.sup.-11 M, about 10.sup.-12 M, about 10.sup.-13 M, about 10.sup.-14 M, about 10.sup.-15 M, and about 10.sup.-16 M. The first or said second relationship can be obtained with use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or chromatography. In some embodiments of the method the first or said second relationship does not involve taking neither real-time measurements nor generation of a standard curve. The standardized mixtures can control for sources of variation such as 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. The standardized mixtures of said series can enumerate less than about 1,000 molecules of said first nucleic acid in one of said samples, less than about 100 molecules of said first nucleic acid in one of said samples, less than about 10 molecules of said first nucleic acid in one of said samples, or about 1 molecule of said first nucleic acid in one of said samples. The standardized mixtures of said series can provide a coefficient of variation of less than about 25%, less than about 15%, or less than about 10% between 2 of said samples comprising said first nucleic acid. The method can be performed on samples obtained from different subjects, different laboratories, or at different times. The method can reduce or eliminate false negatives to an insignificant number, such as to a statistically insignificant number. The method can be computer implemented, the computer implementation comprises instructing a robotic handler to select said first one of said serially-diluted standardized mixtures for combining. The computer implementation can comprise obtaining said first relationship, such as determining an area under a curve. The computer implementation can comprise instructing said robotic handler to select said second one of said serially-diluted standardized mixtures based on said first relationship. The nucleic acid assessed can be an RNA molecule or a DNA molecule. [0009] Another aspect of the invention is a method for preparing a standardized mixture of reagents, said reagents comprising sufficient competitive template for assessing amounts of a number of nucleic acids in more than about 10.sup.6 samples wherein said standardized mixture allows direct comparison of said amounts between 2 of said samples. The number can be two nucleic acids, is at least about 96 nucleic acids, at least about 100 nucleic acids, or at least about 1,000 nucleic acids. The method can involve the use of reagents that are sufficient to assess said amounts in more than about 10.sup.8 samples, more than about 10.sup.10 samples, more than about 10.sup.11 samples, or more than about 10.sup.12 samples. The method can employ reagents which further comprise a forward primer and/or a reverse primer for priming amplification of said competitive template for said number of nucleic acid(s). The competitive template, said forward primer and/or said reverse primer can comprise a sequence referenced in Table 4. The forward primer and/or said reverse primer can have substantially the same annealing temperature as another forward primer and/or reverse primer in said standardized mixture. The forward primer and/or said reverse primer can allow for detection of about 600 molecules or less of said nucleic acid(s), about 60 molecules or less of said nucleic acid(s), or about 6 molecules or less of said nucleic acid(s). At least one of said nucleic acids can comprise a sequence referenced in Table 1 or 2. One of said number of nucleic acids can serve as a first reference nucleic acid. The first reference nucleic acid can be a control for loading and can be GADP, ACTB, or .beta.-actin. Also, another one of said number of nucleic acids serves as a second reference nucleic acid. The second reference nucleic acid can be a gene selected from GADP, ACTB, and .beta.-actin. The assessing can be performed with use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or chromatography. In some embodiments, the does not involve taking neither real-time measurements nor generation of a standard curve. The standardized mixtures can control for sources of variation such as 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. The standardized mixtures of said series can enumerate less than about 1,000 molecules of said first nucleic acid in one of said samples, less than about 100 molecules of said first nucleic acid in one of said samples, less than about 10 molecules of said first nucleic acid in one of said samples, or about 1 molecule of said first nucleic acid in one of said samples. The standardized mixtures of said series can provide a coefficient of variation of less than about 25%, less than about 15%, or less than about 10% between 2 of said samples comprising said first nucleic acid. The method can be performed on samples obtained from different subjects, different laboratories, or at different times. The method can reduce or eliminate false negatives to an insignificant number, such as to a statistically insignificant number. The nucleic acid assessed can be an RNA molecule or a DNA molecule. [0010] Another aspect of the invention is a method comprising preparing a series of serially-diluted standardized mixtures of reagents, said reagent comprising sufficient competitive template for assessing amounts of a number of nucleic acids in more than about 10.sup.6 samples wherein said standardized mixtures allow direct comparison of said amounts between 2 of said samples. The number can be two nucleic acids, is at least about 96 nucleic acids, at least about 100 nucleic acids, or at least about 1,000 nucleic acids. The method can involve the use of reagents that are sufficient to assess said amounts in more than about 10.sup.8 samples, more than about 10.sup.10 samples, more than about 10.sup.11 samples, or more than about 10.sup.12 samples. In some methods, the amounts can vary over a range of more than about 2 orders of magnitude, over a range of about 3 or more orders of magnitude, over a range of about 4 or more orders of magnitude, over a range of about 6 or more orders of magnitude, or over a range of about 7 or more orders of magnitude. The series can allow for detection of less than about a two-fold difference over said range, of less than about a 50% difference over said range, of less than about a 20% difference over said range. Also, about 8 or more orders of magnitude, about 9 or more orders of magnitude, about 10 or more orders of magnitude, or about 15 or more orders of magnitude are encompassed herein. The about 7 orders of magnitude can span about a 7-log range of gene expression and can include about 10.sup.-3, about 10.sup.-2, about 0.1, about 1, about 10, about 10.sup.2, about 10.sup.3, and about 10.sup.4 copies/cell. The method can employ reagents which further comprise a forward primer and/or a reverse primer for priming amplification of said competitive template for said number of nucleic acid(s). The competitive template, said forward primer and/or said reverse primer can comprise a sequence referenced in Table 4: The forward primer and/or said reverse primer can have substantially the same annealing temperature as another forward primer and/or reverse primer in said standardized mixture. The forward primer and/or said reverse primer can allow for detection of about 600 molecules or less of said nucleic acid(s), about 60 molecules or less of said nucleic acid(s), or about 6 molecules or less of said nucleic acid(s). At least one of said nucleic acids can comprise a sequence referenced in Table 1 or 2. The competitive templates can comprise a first competitive template for a first one of said nucleic acids and a second competitive template for a second one of said nucleic acids wherein said first competitive template is at a series of concentrations relative to said second competitive template. The second nucleic acid can serve as a first reference nucleic acid, such as a control for loading and be GADP, ACTB, or .beta.-actin. In the method the series of concentrations can provide 10-fold serial dilutions of said first competitive template relative to said second competitive template. At least two of said series of concentrations span about one order of magnitude, about three orders of magnitude, or about 6 orders of magnitude. The series of concentrations can include concentrations selected from about 10.sup.-11 M, about 10.sup.-12M, about 10.sup.-13 M, about 10.sup.-14 M, about 10.sup.-15 M, and about 10.sup.-16 M. The assessing can be performed with use of microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or chromatography. In some embodiments, the does not involve taking real-time measurements nor generation of a standard curve. The standardized mixtures can control for sources of variation such as 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. The standardized mixtures of said series can enumerate less than about 1,000 molecules of said first nucleic acid in one of said samples, less than about 100 molecules of said first nucleic acid in one of said samples, less than about 10 molecules of said first nucleic acid in one of said samples, or about 1 molecule of said first nucleic acid in one of said samples. The standardized mixtures of said series can provide a coefficient of variation of less than about 25%, less than about 15%, or less than about 10% between 2 of said samples comprising said first nucleic acid. The method can be performed on samples obtained from different subjects, different laboratories, or at different times. The method can reduce or eliminate false negatives to an insignificant number, such as to a statistically insignificant number. The nucleic acid assessed can be an RNA molecule or a DNA molecule. [0011] Another aspect of the invention is compositions for use in the methods described herein. One embodiment is a composition comprising a standardized mixture of reagents, said reagents comprising sufficient competitive template for assessing amounts of a number of nucleic acids in more than about 10.sup.6 samples wherein said standardized mixture allows direct comparison of said amounts between 2 of said samples. Another embodiment is a composition comprising a series of serially-diluted standardized mixtures of reagents, said reagent comprising sufficient competitive template for assessing amounts of a number of nucleic acids in more than about 10.sup.6 samples wherein said standardized mixtures allow direct comparison of said amounts between 2 of said samples. [0012] Another aspect of the invention is 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. In the database the number can be at least about 10 samples, at least about 100 samples, at least about 1,000 samples, at least about 5,000 samples, or at least about 10,000 samples. The samples can be obtained from different subjects, from different species, from different laboratories, or at different times. In the database the amounts can show a coefficient of variation of less than about 25%, less than about 20%, less than about 15%, less than about 10%, or less than about 5% between said 2 samples. The database can further comprise numerical values corresponding to amounts of a number of other nucleic acid(s) in said number of samples. The number can be at least about 100 other nucleic acids, at least about 1,000 other nucleic acids, or at least about 10,000 other nucleic acids. The amounts can be obtained using microfluidic capillary electrophoresis, an oligonucleotide array, mass spectrometry, or chromatography. In some embodiments, the amounts are not obtained using neither real-time measurements nor generation of a standard curve. The numerical values can be corrected for sources of variation such as 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. The numerical values typically correspond to numbers of molecules of said first nucleic acid in said number of samples. In the database, at least one of said numerical values can correspond to less than about 1,000 molecules, less than about 100 molecules, less than about 10 molecules, or to about 1 molecule of said first nucleic acid in at least one of said samples. The numerical values can correspond to less than about a two-fold difference or less than about a one-fold difference in said first nucleic acid between 2 of said samples. The numerical values can correspond to less than about an 80% difference, less than about a 50% difference, less than about a 30% difference, or less than about a 20% difference in said first nucleic acid between 2 of said samples. The numerical values can vary over a range of more than about 2 orders of magnitude, over a range of about 4 or more orders of magnitude, over a range of about 6 or more orders of magnitude, or over a range of about 7 or more orders of magnitude. The about 7 orders of magnitude can span about a 7-log range of gene expression to magnitude include about 10.sup.-3, about 10.sup.-2, about 0.1, about 1, about 10, about 10.sup.2, about 10.sup.3, and about 10.sup.4 copies/cell. The numerical values typically do not comprise a statistically significant number of false positives. The numerical values can be used in at least one stage of drug development selected from drug target screening, lead identification, pre-clinical validation, clinical trial and patient treatment. The pre-clinical validation can be a bioassay and/or an animal study. In some embodiments, the direct comparison in the database does not use a bioinformatics resource. The nucleic acid comprises an RNA molecule or a DNA molecule. The database can indicate a gene expression level corresponding to a biological state, such as a normal state or a disease state. [0013] In some embodiments, the database comprises numerical indices, said numerical indices obtained by mathematical computation of 2 numerical values, said 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. The numerical indices can indicate a biological state. In some embodiments, at least one numerical index is a balanced numerical index. The numerical index can be 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. The numerator can correspond to a gene positively associated with said biological state and said denominator corresponds to a gene negatively associated with said biological state. In the database, said biological state can be 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, a drug toxicity, or a predisposition to a drug toxicity. [0014] Yet another aspect of the invention is 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. The method of determining said mathematic computation can involve a use of software. The 2 nucleic acids can be associated with said first biological state and not with said second biological state. The 2 nucleic acids can be positively associated with said first biological state and the other of said 2 nucleic acids is negatively associated with said first biological state. The mathematical computation can comprise 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. The first biological state can be a disease state and said second biological state is a non-disease state. The can be 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. In some embodiments, direct comparison does not use a bioinformatics resource. [0015] Another embodiment is a method comprising 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. [0016] Yet another embodiment is 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. [0017] Yet another embodiment is 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. [0018] Other aspects of the invention include business methods. One embodiment is 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. The first and said second samples can be measured at different times or in different laboratories. The second sample can be obtained from said first specimen or a second specimen. The first and said second specimens can be collected from different subjects or from different species. The measuring step can be performed at least about 100 times per day, at least about 1,000 times per day, or at least about 4,000 times per day. The first specimen can comprise at least about 1,000 cells. The first specimen can comprise a human specimen, which can be collected without identifying information. The collecting information can comprise attesting to compliance with investigative protocol. The identifying information can be collected at a later time than said collection of said first specimen. The information can be collected via a website. The method can further comprise identifying which of said selected nucleic acids electrophorese together. The amounts of said identified nucleic acids can be electrophoresed simultaneously. The numerical value can be provided via e-mail. The assessing can comprise 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. The first nucleic acid and said competitive template for said first nucleic acid can be co-amplified in a first vessel and said second nucleic acid and said competitive template for said second nucleic acid are co-amplified in a second vessel. The method can further comprise 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. The second nucleic acid can serve as a reference nucleic acid. The standardized mixture can further comprise sufficient amounts of said competitive templates for assessing said first nucleic acid in more than about 106 samples. [0019] Business methods for drug development are also provided herein. One embodiments is 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. Another embodiment is 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. The first or said second biological entity is typically 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. The first or said second stage of drug development can be drug target screening, lead identification, pre-clinical validation, clinical trial and/or patient treatment. The pre-clinical validation can be a bioassay and/or an animal study. The altering can comprise a stratification of a clinical trial. The stratification can involve identifying subjects to have a reduced side effect. The altering can reduce the time for said drug development. [0020] Yet another embodiment is 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. BRIEF DESCRIPTION OF THE FIGURES [0021] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the objects, features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: Continue reading about Databases for assessing nucleic acids... Full patent description for Databases for assessing nucleic acids Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Databases for assessing nucleic acids patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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