Method for determining sequence alignment significance
AssigneeEidogen, Inc.
InventorAleksandar Poleksic
Life of this patent
Estimating the term…
Abstract
The present invention relates to methods and systems for quickly determining the statistical significance of a raw alignment score produced by aligning a first sequence to a second sequence. The claimed methods and systems determine multiple estimates of the p-value of an alignment score. Each p-value estimate is then compared to a pre-defined threshold p-value. Depending upon the claimed method employed and further depending upon whether a particular p-value estimate is less than/greater than the threshold p-value, a raw alignment score may be considered statistically significant or insignificant.
Claims57
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x, P(x|KN1,K,λ(j)N1,λ) using the Island method wherein KN1,K is determined using N1,K islands, λ(j)N1,λ is determined using N1,λ islands and j≧3;
- c. comparing P(x|KN1,K,λ(j)N1,λ+) to Pth;
- and
- d. if P(x|KN1,K,λ(j)N1,λ+)>Pth, determining said alignment score is statistically insignificant, otherwise, determining said alignment score may or may not be statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x, P(x|KN1,K,λ(j)N1,λ+), using the Island method wherein KN1,K is determined using N1,K islands, λ(j)N1,λ+ is determined using N1,λ islands and j≧3;
- c. comparing P(x|KN1,K,λ(j)N1,λ+) to Plh;
- d. if P(x|KN1,K,λ(j)N1,λ+)≦Pth, determining a second estimate of the p-value of said alignment score x, P(x|KN2,K,λ(j)N2,λ+) using the Island method wherein KN2,K is determined using N2,K≧9000 islands, λ(j)N2,λ+ is determined using N2,λ≧9000 islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- e. comparing P(x|KN2,K,λ(j)N2,λ+) to Pth;
- and
- f. if P(x|KN2,K,λ(j)N2,λ+)≦Pth, determining said alignment score is statistically significant, otherwise, determining said alignment score is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x, P(x|KN1,K,λ(j)N2,λ+), using the Island method wherein KN1,K is determined using N1,K islands, λ(j)N1,λ+ is determined using N1,λ islands and j≧3;
- c. comparing P(x|KN1,K,λ(j)N1,λ+) to Pth
- d. if P(x|KN1,K,λ(j)N1,λ+)≦Pth, determining a second estimate of the p-value of said alignment score x, P(x|KN2,K,λ(j)N2,λ+), using the Island method wherein KN2,K is determined using N2,K islands, λ(j)N2,λ+ is determined using N2,λ islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- e. repeating steps c) and d) until determining a final estimate of the p-value of said alignment score, P(x|KNfinal,K,λ(j)Nfinal,λ+), using the, Island method wherein KNfinal,K is determined using Nfinal,K≧9000 islands, λ(j)Nfinal,λ+ is determined using Nfinal,λ≧9000 islands and j≧3;
- f. comparing P(x|KNfinal,K,λ(j)Nfinal,λ+) to Pth;
- and
- g. if P(x|KNfinal,K,λ(j)Nfinal,λ+)≦Pth determining said alignment score x is statistically significant, otherwise determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x, P(x|KN1,λ(j)N1+), using the Island method wherein KN1 and λ(j)N1+ are each determined using N1 islands and j>3;
- C. comparing P(x|KN1,λ(j)N1+) to Pth;
- d. if P(x|KN1,λ(j)N1+)≦Pth, determining a second estimate of the p-value of said alignment score x, P(x|KN2,λ(j)N2+), using the Island method wherein KN2 and λ(j)N2+ are each determined using N2 islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- e. repeating steps c) and d) until determining a final estimate of the p-value of said alignment score, P(x|KNfinal,λ(j)Nfinal), using the Island method wherein KNfinal and λ(j)Nfinal+ are each determined using Nfinal≧9000 islands and j≧3, otherwise;
- f. comparing P(x|KNfinal,λ(j)Nfinal+) to Pth;
- and
- g. if P(x|KNfinal,λ(j)Nfinal+)≦Pth, determining said alignment score x is statistically significant, otherwise determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x, P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+), using the Island method wherein K(λ(j)N1,λ+)N1,K− is determined using N1,K islands, λ(j)N1,λ is determined using N1,λ islands and j≧3;
- c. comparing P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+) to Pth;
- and
- d if P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+)>Pth, determining said alignment score x is statistically insignificant, otherwise, determining said alignment score may or may not be statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x, P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+), using the Island method wherein K(λ(j)N1,λ+)N1,K− is determined using N1,K islands, λ(j)N1,λ is determined using N1,λ islands and j≧3;
- C. comparing P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+) to Pth;
- d. if P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+)≦Pth, determining a second estimate of the p-value to said alignment score x, P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N2,λ+), using the Island method wherein K(λ(j)N2,λ+)N2,K− is determined using N2,K≧9000 islands, λ(j)N2,λ+ is determined using N2,λ≧9000 islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- e. comparing P(x|K(λ(j)N2,λ)N2,K−,λ(j)N2,λ+) to Pth;
- and
- if P(x|K(λ(j)N2,λ)N2,K−,λ(j)N2,λ+)≦Pth, determining said alignment score x is statistically significant, otherwise determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x P(x|K(λ(j)N1,λ+)N1,K−, λ(j)N1,2+), using the Island method wherein K(λ(j)N1,λ+)N1,K− is determined using N1,K islands, λ(j)N1,λ+ is determined using N1,λ islands and j≧3;
- c. comparing P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+) to Pth;
- d) if P(x|K(λ(j)N1,λ+)N1,K−,λ(j)N1,λ+)≦Pth, determining a second estimate of the p-value to said alignment score x, P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N2,λ+) using the Island method wherein K(λ(j)N2,λ+)N2,K−, is determined using N2,K islands, λ(j)N2,λ+ is determined using N2,λ islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- e) repeating steps c) and d) until determining a final estimate of the p-value of said alignment score x, P(x|K(λ(j)Nfinal,λ+)Nfinal,K−λ(j)Nfinal,λ+), using the Island method wherein K(λ(j)Nfinal,λ+)Nfinal,K−is determined using Nfinal,K≧9000 islands, λ(j)Nfinal,λ+ is determined using Nfinal,λ≧9000 islands and j≧3;
- f) comparing P(x|K(λ(j)Nfinal,λ+)Nfinal,K−λ(j)Nfinal,λ+) to Pth;
- and
- g) if P(x|K(λ(j)Nfinal,λ+)Nfinal,K−λ(j)Nfinal,λ+)≦Pth determining said alignment score x is statistically significant, otherwise determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x P(x|K(λ(j)N+)N1−,λ(j)N1+), using the Island method wherein K(λ(j)N1+)N1− and λ(j)N1+ are each determined using N1 islands and j≧3;
- c. comparing P(x|K(λ(j)N1+)N1−,λ(j)N1+) to Pth;
- d. if P(x|K(λ(j)N1+)N1−,λ(j)N1+)≦Pth, determining a second estimate of the p-value to said alignment score x. P(x|K(λ(j)N2+)N2−,λ(j)N2+) using the Island method wherein K(λ(j)N2+)N2− and λ(j)N2+ are each determined using N2 islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- e) repeating steps c) and d) until determining a final estimate of the p-value of said alignment score x, P(x|K(λ(j)Nfinal+)Nfinal−,λ(j)Nfinal+), using the Island method wherein K(λ(j)Nfinal+)Nfinal− and λ(j)Nfinal+ are each determined using Nfinal≧9000 islands and j≧3;
- f) comparing P(x|K(λ(j)Nfinal+)Nfinal−,λ(j)Nfinal+) to Pth;
- and
- g) if P(x|K(λ(j)Nfinal+)Nfinal−,λ(j)Nfinal+)≦Pth determining said alignment score x is statistically significant, otherwise determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x P(x|K(λ(j)N1,λ+)N1,K+λ(j)N1,λ−), using the Island method wherein K(λ(j)N1,λ+)N1,K+ is determined using N1,K islands, λ(j)N1,λ+ and λ(j)N1,λ+ are each determined using N1,λ islands and j≧3
- c. comparing P(x|K(λ(j)N1,λ+)N1,K+,λ(j)N1,λ−) to Pth;
- d. if P(x|K(λ(j)N1,λ+))N1,K+,λ(j)N1,λ−)>Pth, determining a second estimate of the p-value to said alignment score x, P(x|K(λ(j)N2,λ+)N2,K+,λ(j)N2,λ+), using the Island method wherein K(λ(j)N2,λ+)N2,K− is determined using N2,K=N1,K islands, λ(j)N2,λ+ is determined using N2,λ=N1,λ islands and j≧3, otherwise, determining said alignment score x is statistically significant;
- e. comparing P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N1,λ+) to Pth;
- f if P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N1,λ+)≦Pth, determining a third estimate of the p-value of said alignment score x, P(x|K(λ(j)N3,λ+)N3,K−,λ(j)N3,λ+) using the Island method wherein K(λ(j)N3,λ+)N3,K+ is determined using, N3,λ≧9,000 islands, λ(j)N3λ− and λ(j)N3,λ+ are each determined using N3,λ≧9,000 islands and j≦3, otherwise, determining said alignment score x is statistically insignificant;
- g. comparing P(x|K(λ(j)N3,λ+)N3,K+,λ(j)N3,λ−) to p and
- h. if P(x|K(λ(j)N3,λ+)N3,K+,λ(j)N3,λ−)≦Pth, determining said alignment score x is statistically significant, otherwise, determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x P(x|K(λ(j)N1,λ+)N1,K+,λ(j)N1,λ−), using the Island method wherein K(λ(j)N1,λ+)N1,K+ is determined using N1,K islands, λ(j)N1,λ− and λ(j)N1,λ+ are each determined using N1,λ islands and j≦3
- C. comparing P(x|K(λ(j)N1,λ+)N1,K+,λ(j)N1,λ−)
- d. if P(x|K(λ(j)N1,λ)N1,K,λ(j)N1,λ−)>Pth, determining a second estimate of the p-value of said alignment score x, P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N2,λ+, using the Island method wherein K(λ(j)N2,λ+)N2,K− is determined using N2,K×N1,K islands, λ(j)N2,λ+ is determined using N2,λ×N1,λ islands and j≧3, otherwise, determining said alignment score x is statistically significant;
- e. comparing P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N2λ+) to Pth;
- f. if P(x|K(λ(j)N2,λ+)N2,K−,λ(j)N2λ+)≦Pth,determining a third estimate of the p-value of said alignment score x, P(x|K(λ(j)N3,λ+)N3,K+,λ(j)N3,λ−), using the Island method wherein K(λ(j)N3,λ+)N3,K+ is determined using N3,K islands, λ(j)N3,λ+ and λ(j)N3,λ− are each determined using N3,λ islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- g. repeating steps c)-f) until determining a final estimate of the p-value of said alignment score x, P(x|K(λ(j)Nfinal,λ+)Nfinal,K+,λ(j)Nfinal,λ−), using the Island method wherein K(λ(j)Nfinal,λ+)Nfinal,K+ is determined using Nfinal,K≧9000 islands, λ(j)Nfinal,λ− and λ(j)Nfinal,λ+ are each determined using Nfinal,λ≧9000 islands and j≧3;
- h. comparing P(x|K(λ(j)Nfinal,λ+))Nfinal,K+,λ(j)Nfinal,λ−) to Pth;
- and
- i. if P(x|K(λ(j)Nfinal,λ+)Nfinal,K+,λ(j)Nfinal,λ−)≦Pth, determining said alignment score x is statistically significant, otherwise, determining said alignment score x is statistically insignificant.
A method for determining whether an alignment score x, determined from the alignment of a first sequence with a second sequence, is statistically significant or insignificant comprising the steps of:
- a. determining a threshold p-value, Pth;
- b. determining a first estimate of the p-value of said alignment score x P(x|K(λ(j)N1+)N1+,λ(j)N1−), using the Island method wherein K(λ(j)N1+)N1+,λ(j)N1+) and λ(j)N1− are each determined using N1 islands and j>3;
- c. comparing P(x|K(λ(j)N1+)N1+,λ(j)N1−) to Pth;
- d. if P(x|K(λ(j)N1+)N1+,λ(j)N1−)>Pth, determining a second estimate of the p-value of said alignment score x, P(x|K(λ(j)N2+)N2−,λ(j)N2+), using the Island method wherein K(λ(j)N2+)N2− and λ(j)N2+ are each determined using N2=N1, islands and j≧3, otherwise, determining said alignment score x is statistically significant;
- e. comparing P(x|K(λ(j)N2+)N2−,λ(j)N2+) to Pth if P(x|K(λ(j)N2+)N2−,λ(j)N2+)≦Pth, determining a third estimate of the p-value of said alignment score x, P(x|K(λ(j)N3+)N3+,λ(j)N3−), using the Island method wherein K(λ(j)N3+)N3+,λ(j)N3+ and λ(j)N3− are each determined using N3 islands and j≧3, otherwise, determining said alignment score x is statistically insignificant;
- g. repeating steps c)-f) until determining a final estimate of the p-value of said alignment score x, P(x|K(λ(j)Nfinal+)Nfinal+,λ(j)Nfinal−), using the Island method wherein K(λ(j)Nfinal+)Nfinal+,λ(j)Nfinal− and λ(j)Nfinal− are each determined using Nfinal≧9000 islands and j≧3;
- h. comparing P(x|K(λ(j)Nfinal+)Nfinal+,λ(j)Nfinal−) to Pth and
- i. if P(x|K(λ(j)Nfinal+)Nfinal+,λ(j)Nfinal−)≦Pth, determining said alignment score x is statistically significant, otherwise, determining said alignment score x is statistically insignificant.
Dependencies are inferred from the claim text.