METHODS AND COMPOSITIONS FOR ARRAY-BASED COUNTING
Methods, kits, and systems are disclosed for array-based counting. The method generally comprises obtaining data pertaining to one or more probes on an array and conducting probe-specific analysis of the data to determine a count of one or more objects hybridized to the probe on the array. The probe-specific analysis may comprise modeling a behavior of one or more probes. The objects hybridized to the probe may be nucleic acids from a sample. The sample may comprise a total quantity of nucleic acids of less than one genome equivalent. The array may be a tiling array. The methods, kits, and systems may be used for quantifying samples comprising low quantities of nucleic acids. The methods, kits, and systems may be used to diagnose a disease or condition in a subject. The methods, kits, and systems may be used to diagnose a fetal disorder.
1 . A method comprising:
a. hybridizing a plurality of nucleic acids from a sample to one or more probes on an array to produce one or more hybridized nucleic acids, wherein the plurality of nucleic acids comprise one or more molecular species;
b. scanning the array to obtain a detection signal for the one or more probes;
c. converting the detection signal to a digital signal; and
d. determining a count of the one or more hybridized nucleic acids based on a count of the digital signal.
2 . The method of claim 1 , wherein the detection signal is an intensity signal.
3 . The method of claim 2 , wherein converting the detection signal to a digital signal comprises binary classification of the detection signal.
4 . The method of claim 3 , wherein the binary classification comprises classifying a probe as positive or negative.
5 . The method of claim 4 , wherein determining the count of the one or more hybridized nucleic acids comprises determining a count of probes that are classified as positive.
6 . The method of claim 1 , wherein converting the detection signal to a digital signal comprises modeling a behavior of the one or more probes based on the sequence of the probe.
7 . The method of claim 6 , wherein modeling the behavior of the one or more probes comprises applying an algorithm to the detection signal.
8 . (canceled)
9 . The method of claim 6 , wherein modeling the behavior of the one or more probes comprises subtracting a probe-specific background from the detection signal of the probe.
10 . The method of claim 6 , wherein modeling the behavior of the one or more probes comprises clustering the probes into groups based on similarity of one or more features.
11 . (canceled)
12 . The method of claim 1 , wherein the array is a microarray or a titling array.
13 . (canceled)
14 . The method of claim 1 , wherein the array comprises a plurality of probes.
15 . (canceled)
16 . (canceled)
17 . The method of claim 16 , wherein the plurality of probes is capable of hybridizing to the one molecular species.
18 . The method of claim 17 , wherein the plurality of probes is capable of hybridizing to one or more regions on the one molecular species.
19 . The method of claim 17 , wherein the plurality of probes is capable of hybridizing to two or more regions on the one molecular species.
20 . (canceled)
21 . (canceled)
22 . The method of claim 14 , wherein at least two probes of the plurality of probes are different.
23 . The method of claim 14 , wherein at least two probes of the plurality of probes are less than 90% identical.
24 . (canceled)
25 . (canceled)
26 . The method of claim 16 , wherein the plurality of probes is capable of hybridizing to two or more molecular species.
27 . The method of claim 14 , wherein the plurality of probes comprises two or more sets of probes.
28 . The method of claim 27 , wherein the two or more sets of probes are capable of hybridizing to one molecular species.
29 . The method of claim 27 , wherein the two or more set of probes are capable of hybridizing to two or more molecular species.
30 .- 215 . (canceled)