Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are currently pending and under exam herein.
Claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are rejected.
Claims 6, 8, 16, 19-23, 25, 29-35, 37-38
Priority
The instant application claims priority from provisional 63/089,432 filed on 10/08/2020. Thus, the effective filing date of the instant application is 10/08/2020
Drawings
The Drawings filed on 04/07/2023 were considered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/16/2023, 03/03/2026, 05/27/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Regarding claim 9, the phrase "(e.g., 26 bp)" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 12, the phrase "(e.g., hash table)" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 15, the phrase "(e.g., 26 bp)" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite: (a) mathematical concepts, (e.g., mathematical relationships, formulas or equations, mathematical calculations); and (b) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgement, opinion).
Subject matter eligibility evaluation in accordance with MPEP 2106:
Eligibility Step 1: Claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are directed to methods, systems and devices for processing sequence data
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if
so, then it is determined in Prong Two whether the recited judicial exception is integrated into a
practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception,
examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a
law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
Independent claim 1 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
performing a plurality of adapter trimming passes, the adapter trimming passes comprising at least (mathematical concept, mental process)
a first trimming pass, for each sequencing read, starting at a base pair (bp) that is 1 base greater than the known insert length, comprising removing adapter bps from the sequence, which comprises using a first predetermined number of bps of the adapter so as to find a match in the sequence considering a limited plurality of possible overlaps; (mathematical concept, mental process)
after the first trimming pass, if the sequencing read is greater than a predetermined number of bps, performing a limited number of second trimming passes, at any place along the sequencing read, each comprising matching one or more adapters at the first predetermined number of bp of the adapter plus or minus a predetermined number of additional bps from a prior trimming pass, wherein: (mathematical concept, mental process, contingent limitation)
the limited number of trimming passes result each single-ended read is ultimately trimmed to a single-ended specific number of bps, and each paired-end read is ultimately trimmed to a paired-end specific number of bps; and (mathematical concept, mental process, contingent limitation)
optionally re-labeling an insert bps using information from one or more trimming passes. (mathematical concept, mental process, contingent limitation)
Dependent claim 2 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the first trimming pass is started at bp 27. (mathematical concept, mental process)
Dependent claim 3 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the first trimming pass is only performed if the sequencing read is at least 36 bps in length. (mathematical concept, mental process)
Dependent claim 4 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein with the first trimming pass, the first predetermined number of bps of the adapter comprises 10 bps. (mathematical concept, mental process)
Dependent claim 5 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the predetermined number of additional bps comprises between 1 and 2 bps.
Dependent claim 7 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
comprising reading a plurality of sequencing reads from one or more sequencing data files (“SDF”), wherein: (mathematical concept)
the plurality of sequencing reads comprise a plurality of single-ended reads and a plurality of paired-end reads, each single-ended read comprises a single SDF (“R1”), and each paired-end read comprises two SDFs (“R1”, “R2”), for a paired-end read, a first R1 of the two SDFs comprising a forward read of the paired-ended read, and a second R2 of the two SDFs comprising a reverse read of the paired-ended read (mathematical concept)
each SDF comprising 4 lines of information, a second line thereof comprising sequencing data, and a fourth line thereof comprising quality scores for the sequencing data; (mathematical concept)
the sequencing data of each read comprising insert data associated with base pairs (“bps”) of an insert (i.e., a DNA fragment), and second adapter data associated with bps of an associated adapter on an end of the insert; and/or (mathematical concept)
for a paired-end, the sequence line of R1 is from base pair (“bp”) 1 to a last bp, and the sequence line of R2 is from the last bp to bp 1. (mathematical concept)
Dependent claim 9 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
further comprising performing at least one additional processing step on the plurality of sequencing reads, wherein the at least one additional processing step is selected from the group consisting of: stitching, extracting, first matching, deduplication, and second matching (mathematical concept)
Dependent claim 10 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the stitching comprises: for each paired end read, overlapping a first sequencing read (R1) of the paired-end read with a second sequencing read (R2) of the paired-end read and comparing the overlapped portions, (mathematical concept)
wherein upon the reads not matching, selecting one of R1 and R2 having a higher quality score, or should the quality scores be equal: (mathematical concept)
calculating at least one regional score for R1 and R2 progressively until one of R1 and R2 has a higher quality score, wherein calculating comprises adding quality score values for the non-matching bp, one bp to the left of the non-matching bp, and one bp to the right of each of R1 and R2, selecting the read having the higher total quality score, and (mathematical concept)
trimming the selected read to a predetermined number of bp (e.g., 26 bp) using numbering from R1. (mathematical concept)
Dependent claim 11 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the extracting comprises splitting each read into a unique molecular identifier (“UMI”), and barcode. (mathematical concept)
Dependent claim 12 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the first matching comprises matching each read against a library (e.g., hash table) of expected bar codes with a given error rate.
Dependent claim 13 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein, with respect to the first matching: if a barcode from a read is shorted, a last bp will be accorded as an “N”, so a remaining predetermined number of bps match exactly to an identifier in the library, if an exact match for bar code is specified, the predetermined number of bps match of a read is not performed; and if a match is not found, the read is saved in memory. (mathematical concept)
Dependent claim 14 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the second matching comprises, for each barcode not matched via alignment matching (“NMBC”), matching the UMI of the NMBC amongst UMIs of previously matched barcodes via alignment matching, wherein if a UMI is found, the NMBC is compared to the barcode of the found UMI to confirm a match, allowing a plurality of mis-matched bps. (mathematical concept)
Independent claim 15 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
for each paired end read, overlapping a first sequencing read (R1) of a paired-end read with a second sequencing read (R2) of a paired-end read and comparing the overlapped portions (mathematical concept),
wherein upon the reads not matching selecting one of R1 and R2 having a higher quality score, or should the quality scores be equal: (mathematical concept)
calculating at least one regional score for R1 and R2 progressively until one of R1 and R2 has a higher quality score, wherein calculating comprises adding quality score values for the non-matching bp, one bp to the left of the non-matching bp, and one bp to the right of each of R1 and R2, selecting the read having the higher total quality score, and (mathematical concept)
trimming the selected read to a predetermined number of bp (e.g., 26 bp) using numbering from R1. (mathematical concept)
Dependent claim 17 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
further comprising performing at least one additional processing step on the plurality of sequencing reads, the at least one additional processing step selected from the group consisting of: adapter trimming, extracting, first matching, deduplication, and second matching (mathematical concept)
Dependent claim 18 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the adapter trimming comprises at least: a first trimming pass, for each sequencing read, starting at a bp that is 1 base greater than the known insert length, comprising removing adapter bps from the sequence, which comprises using a first predetermined number of bps of the adapter so as to find a match in the sequence considering a limited plurality of possible overlaps (mathematical concept)
after the first trimming pass, if the read is greater than a predetermined number of bps, performing a limited number of second trimming passes, at any place along the read, each comprising matching one or more adapters at the first predetermined number of bp of the adapter plus or minus a predetermined number of additional bps from a prior trimming pass, wherein: (mathematical concept)
the limited number of trimming passes result each single-ended read is ultimately trimmed to a single-ended specific number of bps, and each paired-end read is ultimately trimmed to a paired-end specific number of bps; and (mathematical concept)
optionally re-labeling the/an insert bps using information from one or more trimming passes (mathematical concept)
Dependent claim 24 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein: the plurality of sequencing reads comprise a plurality of single-ended reads and a plurality of paired-end reads, (mathematical concept)
each single-ended read comprises a single SDF (“R1”), and each paired-end read comprises two SDFs (“R1”, “R2”), for a paired-end read, a first R1 of the two SDFs comprising a forward read of the paired-ended read, and a second R2 of the two SDFs comprising a reverse read of the paired-ended read; each SDF comprising 4 lines of information, a second line thereof comprising sequencing data, and a fourth line thereof comprising quality scores for the sequencing data; (mathematical concept)
the sequencing data of each read comprising insert data associated with basepairs (“bps”) of an insert (i.e., a DNA fragment), and second adapter data associated with bps of an associated adapter on an end of the insert; and/or (mathematical concept)
for a paired-end, the sequence line of R1 is from basepair (“bp”) 1 to a last bp, and the sequence line of R2 is from the last bp to bp 1. (mathematical concept)
Dependent claim 26 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the first matching comprises matching each read against a library (e.g., hash table) of expected bar codes with a given error rate. (mathematical concept)
Dependent claim 27 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein, with respect to the first matching: if a barcode from a read is shorted, a last bp will be accorded as an “N”, so a remaining predetermined number of bps match exactly to an identifier in the library, if an exact match for bar code is specified, the predetermined number of bps match of a read is not performed; and if a match is not found, the read is saved in memory. (mathematical concept)
Dependent claim 28 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the second matching comprises for each barcode not matched via alignment matching (“NMBC”), matching the UMI of the NMBC amongst UMIs of previously matched barcodes via alignment matching, wherein if a UMI is found, the NMBC is compared to the barcode of the found UMI to confirm a match, allowing a plurality of mis-matched bps. (mathematical concept)
The MPEP states iv. organizing information and manipulating information through mathematical correlations, Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). The patentee in Digitech claimed methods of generating first and second data by taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form. The court explained that such claims were directed to an abstract idea because they described a process of organizing information through mathematical correlations, like Flook's method of calculating using a mathematical formula. 758 F.3d at 1350, 111 USPQ2d at 1721 and v. using an algorithm for determining the optimal number of visits by a business representative to a client are abstract ideas. For more information see MPEP 2106.04
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pencil and paper, and therefore recite judicial exceptions from the mental process grouping of abstract ideas. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Therefore, claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 recite an abstract idea as the dependent claims will inherit the abstract ideas from the independent claims.
[Step 2A Prong One: YES]
Eligibility Step 2A Prong Two: In determining whether a claim is directed to a judicial exception, further
examination is performed that analyzes if the claim recites additional elements that when examined as a
whole integrates the judicial exception(s) into a practical application (MPEP 2106.04(d)). A claim that
integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception
in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements
are analyzed to determine if the abstract idea is integrated into a practical application (MPEP
2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract
idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)(III)).
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
The additional element in independent claim 1 includes:
A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of reads contained in a sequencing data file, the method comprising
The additional element in dependent claim 15 includes:
A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of sequencing reads contained in one or more sequencing data files (“SDF”), the method comprising a stitching process comprising:
The additional element in dependent claim 36 includes:
A system or device comprising at least one computer processor having access to computer instructions configured to cause a server to perform the method recited in claim 1.
The additional elements of a sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of reads contained in a sequencing data file, the method comprising (Claim 1), a sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of sequencing reads contained in one or more sequencing data files (“SDF”), the method comprising a stitching process comprising (Claim 15), a system or device comprising at least one computer processor having access to computer instructions configured to cause a server to perform the method recited in claim 1 (Claim 36) fail to integrate a judicial exception into a practical application merely reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
Thus, the additionally recited elements merely invoke a computer as a tool, and/or amount to insignificant extra-solution data gathering activity, and as such, when all limitations in claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 have been considered as a whole, the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are directed to an abstract idea (MPEP 2106.04(d)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
The additional elements recited in claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are identified above, and carried over from Step 2A: Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A: Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of a sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of reads contained in a sequencing data file, the method comprising (Claim 1), a sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of sequencing reads contained in one or more sequencing data files (“SDF”), the method comprising a stitching process comprising (Claim 15), a system or device comprising at least one computer processor having access to computer instructions configured to cause a server to perform the method recited in claim 1 (Claim 36) are conventional fail to integrate a judicial exception into a practical application merely reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
Claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 do not recite any elements in addition to the judicial exception. Therefore, when taken alone, all additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as a combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 1-5, 7, 9-15, 17-18, 24, 26-28, 36 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 3, 4, 5, 7, 24, 36, are rejected under 35 U.S.C. 103 as being unpatentable over Bolger et al. (Bolger, A. M.; Lohse, M.; Usadel, B. Trimmomatic: A Flexible Trimmer for Illumina Sequence Data. Bioinformatics 2014, 30 (15), 2114–2120.) in view of Martin et al. (Martin, M. Cutadapt Removes Adapter Sequences from High-Throughput Sequencing Reads. EMBnet.journal 2011, 17 (1), 10) in view of Turner (Turner. Assessment of Insert Sizes and Adapter Content in Fastq Data from NexteraXT Libraries. Frontiers in Genetics 2014.). The italicized text corresponds to the instant claim limitations.
With respect to the limitations of Claims 1, 2, 3, 4, 5, 7, 24, 36, Turner teaches the bases occurring after the i th position of a read (where i is the insert size as calculated in Section “Measurement of Insert Size”) come from the oligo nucleotide attached to the insert. The insert base is therefore i+1. (pg. 3, a first trimming pass, for each sequencing read, starting at a base pair (bp) that is 1 base greater than the known insert length (Claim 1) It is an obvious routine optimization to start the trimming pass at 27 bps. If the oligonucleotide attached to the insert was 26 bps long than the first trim would start at 27 bps when inserting from the 26+1 position. wherein the first trimming pass is started at bp 27 (Claim 2) wherein the first trimming pass is only performed if the sequencing read is at least 36 bps in length (Claim 3), contingent limitation, under the broadest reasonable interpretation it is not needed if the sequencing read is less than 36 bps) low sensitivity of AlienTrimmer for this particular dataset seems to beat least partly due to its poor performance for reads that extended past the length of the fragment. Figure 8 shows how the specificity of cutadapt and AlienTrimmer (for k-mer =10) change depending of the number of bases that need to be trimmed. A predetermined number of 10 was used in this example. (pg. 4, col. 2, wherein with the first trimming pass, the first predetermined number of bps of the adapter comprises 10 bps (Claim 4) wherein the predetermined number of additional bps comprises between 1 and 2 bps (Claim 5, contingent limitation does not need to occur if the sequencing read is less than a predetermined amount of bps.), A system or device comprising at least one computer processor having access to computer instructions configured to cause a server to perform the method recited in claim 1. (Claim 36) Turner also teaches each file contains 4 lines of information each SDF comprising 4 lines of information, a second line thereof comprising sequencing data, and a fourth line thereof comprising quality scores for the sequencing data (pg. 1769, each SDF comprising 4 lines of information, a second line thereof comprising sequencing data, and a fourth line thereof comprising quality scores for the sequencing data (Claim 7, Claim 24) other common steps in a sequencing pipeline include quality and adaptor trimming, and contaminant or quality-based filtering. A set of interchangeable tools like the OBF projects, based on a common FASTQ standard, will be of great benefit here. (pg. 1771, col. 1) Additionally, Claim 7/Claim 24 describes how data is stored in files and is nonfunctional the computer-readable medium merely serves as a support for information or data, no functional relationship exists. For example, a claim to a memory stick containing tables of batting averages, or tracks of recorded music, utilizes the intended computer system merely as a support for the information. Such claims are directed toward conveying meaning to the human reader rather than towards establishing a functional relationship between recorded data and the computer.
See MPEP 2111.05 (further comprising reading a plurality of sequencing reads from one or more sequencing data files (“SDF”), wherein: the plurality of sequencing reads comprise a plurality of single-ended reads and a plurality of paired-end reads, each single-ended read comprises a single SDF (“R1”), and each paired-end read comprises two SDFs (“R1”, “R2”), for a paired-end read, a first R1 of the two SDFs comprising a forward read of the paired-ended read, and a second R2 of the two SDFs comprising a reverse read of the paired-ended read; the sequencing data of each read comprising insert data associated with basepairs (“bps”) of an insert (i.e., a DNA fragment), and second adapter data associated with bps of an associated adapter on an end of the insert; and/or for a paired-end, the sequence line of R1 is from base pair (“bp”) 1 to a last bp, and the sequence line of R2 is from the last bp to bp 1 (Claim 7, Claim 24) after the first trimming pass, if the sequencing read is greater than a predetermined number of bps, performing a limited number of second trimming passes, at any place along the sequencing read, each comprising matching one or more adapters at the first predetermined number of bp of the adapter plus or minus a predetermined number of additional bps from a prior trimming pass, wherein: the limited number of trimming passes result each single-ended read is ultimately trimmed to a single-ended specific number of bps, and each paired-end read is ultimately trimmed to a paired-end specific number of bps; and optionally re-labeling an insert bps using information from one or more trimming passes (Claim 1), contingent limitation, under the broadest reasonable interpretation it is not needed if the sequencing read is less than the predetermined number of bps)
Turner does not explicitly teach
A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of reads contained in a sequencing data file, the method comprising performing a plurality of adapter trimming passes, the adapter trimming passes comprising at least (Claim 1)
removing adapter bps from the sequence, which comprises using a first predetermined number of bps of the adapter so as to find a match in the sequence considering a limited plurality of possible overlaps (Claim 1)
With respect to the limitations of Claims 1, Martin et al. teaches Cutadatpt can search and remove an adapter multiple times, which is useful when (perhaps accidentally) library preparation has led to an adapter being appended multiple times (pg. 2, col. 1, A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of reads contained in a sequencing data file, the method comprising performing a plurality of adapter trimming passes, the adapter trimming passes comprising at least (Claim 1)
With respect to the limitations of Claims 1, Bolger et al. teaches Initial sequence comparisons are done using a 16-base fragment from each sequence which means it takes a fixed-length piece of the adapter and looks for that piece. It also does not try every conceivable alignment but walks the fragment along a defined bounded series of positions from one end to the other. (pg. 2116, col. 1 , removing adapter bps from the sequence, which comprises using a first predetermined number of bps of the adapter so as to find a match in the sequence considering a limited plurality of possible overlaps (Claim 1)
A person of ordinary skill in the art would combine Bolger et al. with Martin et al. with Turner to create an improved method for processing sequence data. All works are in the same field of computational methods for processing and handling sequence data and specifically removing adapter sequences. Each piece supplies a complementary part of a routine workflow. Martin teaches iteratively searching and removing adapters using a fixed portion of the adapter as a search. Bolger teaches seed based adapter detection within a defined series of overlapped positions. Turner teaches when the insert length is known the adapter begins at the next immediate base pair. There is a reasonable expectation of success as each step of the method works independently therefore they are expected to work together. These are well understood methods of processing data, each method works independently so they are expected to and a person of ordinary skill in the art would understand how to combine the different methods to achieve the results.
Claims 9, 10, 11, 15, 17, 18, are rejected under 35 U.S.C. 103 as being unpatentable over Bolger et al. in view of Martin et al. in view of Turner as applied to claims 1, 2, 3, 4, 5, 7, 24, 36, above in further view of Chen et al. (Chen, S.; Zhou, Y.; Chen, Y.; Gu, J. Fastp: An Ultra-Fast All-in-One FASTQ Preprocessor. Bioinformatics 2018, 34 (17), i884–i890.) The italicized text corresponds to the instant claim limitations.
The limitations of Claims 1, 2, 3, 4, 5, 7, 24, 36, have been taught by Bolger et al. in view of Martin et al. in view of Turner above.
With respect to the limitations of Claims 18, Martin et al. teaches Cutadatpt can search and remove an adapter multiple times, which is useful when (perhaps accidentally) library preparation has led to an adapter being appended multiple times (pg. 2, col. 1, A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of reads contained in a sequencing data file, the method comprising performing a plurality of adapter trimming passes, the adapter trimming passes comprising at least (Claim 18)
With respect to the limitations of Claims 18, Turner teaches
The bases occurring after the i th position of a read (where i is the insert size as calculated in Section “Measurement of Insert Size”) come from the oligo nucleotide attached to the insert. The insert base is therefore i+1. (pg. 3, a first trimming pass, for each sequencing read, starting at a base pair (bp) that is 1 base greater than the known insert length (Claim 18)
With respect to the limitations of Claims 18, Bolger et al. teaches
Initial sequence comparisons are done using a 16-base fragment from each sequence which means it takes a fixed-length piece of the adapter and looks for that piece. It also does not try every conceivable alignment but walks the fragment along a defined bounded series of positions from one end to the other. (pg. 2116, col. 1 , removing adapter bps from the sequence, which comprises using a first predetermined number of bps of the adapter so as to find a match in the sequence considering a limited plurality of possible overlaps (Claim 18) after the first trimming pass, if the sequencing read is greater than a predetermined number of bps, performing a limited number of second trimming passes, at any place along the sequencing read, each comprising matching one or more adapters at the first predetermined number of bp of the adapter plus or minus a predetermined number of additional bps from a prior trimming pass, wherein: the limited number of trimming passes result each single-ended read is ultimately trimmed to a single-ended specific number of bps, and each paired-end read is ultimately trimmed to a paired-end specific number of bps; and optionally re-labeling an insert bps using information from one or more trimming passes (Claim 18), contingent limitation, under the broadest reasonable interpretation it is not needed if the sequencing read is less than the predetermined number of bps)
Bolger et al. in view of Martin et al. in view of Turner does not explicitly teach
further comprising performing at least one additional processing step on the plurality of sequencing reads, wherein the at least one additional processing step is selected from the group consisting of: stitching, extracting, first matching, deduplication, and second matching (Claim 9),
further comprising performing at least one additional processing step on the plurality of sequencing reads, the at least one additional processing step selected from the group consisting of: adapter trimming, extracting, first matching, deduplication, and second matching (Claim 17)
wherein the extracting comprises splitting each read into a unique molecular identifier (“UMI”), and barcode (Claim 11
for each paired end read, overlapping a first sequencing read (R1) of the paired-end read with a second sequencing read (R2) of the paired-end read and comparing the overlapped portions (Claim 10), for each paired end read, overlapping a first sequencing read (R1) of a paired-end read with a second sequencing read (R2) of a paired-end read and comparing the overlapped portions (Claim 15
wherein upon the reads not matching, selecting one of R1 and R2 having a higher quality score, or should the quality scores be equal: calculating at least one regional score for R1 and R2 progressively until one of R1 and R2 has a higher quality score, wherein calculating comprises adding quality score values for the non-matching bp, one bp to the left of the non-matching bp, and one bp to the right of each of R1 and R2, selecting the read having the higher total quality score, and trimming the selected read to a predetermined number of bp (e.g., 26 bp) using numbering from R1 (Claim 10, contingent limitation)
A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of sequencing reads contained in one or more sequencing data files (“SDF”), the method comprising a stitching process comprising: wherein upon the reads not matching selecting one of R1 and R2 having a higher quality score, or should the quality scores be equal: calculating at least one regional score for R1 and R2 progressively until one of R1 and R2 has a higher quality score, wherein calculating comprises adding quality score values for the non-matching bp, one bp to the left of the non-matching bp, and one bp to the right of each of R1 and R2, selecting the read having the higher total quality score, and trimming the selected read to a predetermined number of bp (e.g., 26 bp) using numbering from R1 (Claim 15, contingent limitation),
With respect to the limitations of Claims 9, 10, 11, 15, 17, Chen et al. teaches fastp, an ultra-fast tool to perform quality control, read filtering and base correction for FASTQ data. It includes most features of FASTQC + Cutadapt + Trimmomatic + AfterQC while running 2–5 times faster than any of them alone. In addition to the functions available in these tools, fastp offers supplementary features such as unique molecular identifier (UMI) preprocessing, per-read polyG tail trimming and output splitting. fastp also provides quality control reports for pre- and post-filtered data within a single HTML page, which allows for direct comparison of quality statistics altered by preprocessing. fastp can automatically detect adapter sequences for single-end and paired-end Illumina data. In contrast with the aforementioned tools developed in Java or Python, fastp is developed in C/C++ with solid multi-threading implementation, making it much faster than its peers. Furthermore, based on the functions for correcting or eliminating sequencing errors, fastp can obtain even better clean data compared to conventional tools. (pg. i885, further comprising performing at least one additional processing step on the plurality of sequencing reads, wherein the at least one additional processing step is selected from the group consisting of: stitching, extracting, first matching, deduplication, and second matching (Claim 9), further comprising performing at least one additional processing step on the plurality of sequencing reads, the at least one additional processing step selected from the group consisting of: adapter trimming, extracting, first matching, deduplication, and second matching (Claim 17)wherein the extracting comprises splitting each read into a unique molecular identifier (“UMI”), and barcode (Claim 11) Chen et al. teaches fastp supports automatic adapter trimming for both single-end and paired-end Illumina data and uses different algorithms for each of these tasks. For single-end data, adapter sequences are detected by assembling the high-frequency read tails; for paired-end data, adapt er sequences are detected by finding the overlap of each pair (pg. i885 col. 2, for each paired end read, overlapping a first sequencing read (R1) of the paired-end read with a second sequencing read (R2) of the paired-end read and comparing the overlapped portions (Claim 10), for each paired end read, overlapping a first sequencing read (R1) of a paired-end read with a second sequencing read (R2) of a paired-end read and comparing the overlapped portions (Claim 15) Chen et al. teaches fastp evaluates quality scores during overlap analysis for paired-end reads and actively corrects mismatches by favoring the base with the higher quality score, (pg. i885 – i886, wherein upon the reads not matching, selecting one of R1 and R2 having a higher quality score, or should the quality scores be equal: calculating at least one regional score for R1 and R2 progressively until one of R1 and R2 has a higher quality score, wherein calculating comprises adding quality score values for the non-matching bp, one bp to the left of the non-matching bp, and one bp to the right of each of R1 and R2, selecting the read having the higher total quality score, and trimming the selected read to a predetermined number of bp (e.g., 26 bp) using numbering from R1 (Claim 10, contingent limitation) A sequencing data processing method for aiding in the determination of the identity of DNA fragments from a plurality of sequencing reads contained in one or more sequencing data files (“SDF”), the method comprising a stitching process comprising: wherein upon the reads not matching selecting one of R1 and R2 having a higher quality score, or should the quality scores be equal: calculating at least one regional score for R1 and R2 progressively until one of R1 and R2 has a higher quality score, wherein calculating comprises adding quality score values for the non-matching bp, one bp to the left of the non-matching bp, and one bp to the right of each of R1 and R2, selecting the read having the higher total quality score, and trimming the selected read to a predetermined number of bp (e.g., 26 bp) using numbering from R1 (Claim 15, contingent limitation),
A person of ordinary skill in the art would combine Bolger et al. with Martin et al. with Turner with Chen et al. because fastp addresses the same FASTQ preprocessing problem but adds the pair end analysis. Chen even suggests that overlap analysis is beneficial. All works are in the same field of computational methods for processing and handling sequence data and specifically removing adapter sequences. Each piece supplies a complementary part of a routine workflow. Martin teaches iteratively searching and removing adapters using a fixed portion of the adapter as a search. Bolger teaches seed based adapter detection within a defined series of overlapped positions. Turner teaches when the insert length is known the adapter begins at the next immediate base pair. There is a reasonable expectation of success as each step of the method works independently therefore they are expected to work together. These are well understood methods of processing data, each method works independently so they are expected to and a person of ordinary skill in the art would understand how to combine the different methods to achieve the results.
Claims 12, 13, 26, 27, are rejected under 35 U.S.C. 103 as being unpatentable over Bolger et al. in view of Martin et al. in view of Turner in view of Chen et al. as applied to claims 1, 2, 3, 4, 5, 7, 24, 36, 9, 10, 11, 15, 17, 18, above in further view of Schubert et al. (Schubert, M.; Lindgreen, S.; Orlando, L. AdapterRemoval V2: Rapid Adapter Trimming, Identification, and Read Merging. BMC Research Notes 2016, 9 (1)) The italicized text corresponds to the instant claim limitations.
The limitations of claims 1, 2, 3, 4, 5, 7, 24, 36, 9, 10, 11, 15, 17, 18 have been taught by Bolger et al. in view of Martin et al. in view of Turner in view of Chen et al. above.
Bolger et al. in view of Martin et al. in view of Turner in view of Chen et al. does not explicitly teach
wherein the first matching comprises matching each read against a library (e.g., hash table) of expected bar codes with a given error rate (Claim 12, Claim 26),
wherein, with respect to the first matching: if a barcode from a read is shorted, a last bp will be accorded as an “N”, so a remaining predetermined number of bps match exactly to an identifier in the library, if an exact match for bar code is specified, the predetermined number of bps match of a read is not performed; and if a match is not found, the read is saved in memory (Claim 13, Claim 27, contingent limitation not needed as they are if clauses)
With respect to the limitations of Claims 12, 13, 26, 27, Schubert et al. teaches AdapterRemoval v2 further allows for simultaneous demultiplexing and adapter trimming, using a simple maximum-number-of mismatches comparison for the provided barcodes, and correctly trims paired-end reads extending past the end of the insert. (pg. 2, col. 1, paragraph 3, wherein the first matching comprises matching each read against a library (e.g., hash table) of expected bar codes with a given error rate (Claim 12, Claim 26), wherein, with respect to the first matching: if a barcode from a read is shorted, a last bp will be accorded as an “N”, so a remaining predetermined number of bps match exactly to an identifier in the library, if an exact match for bar code is specified, the predetermined number of bps match of a read is not performed; and if a match is not found, the read is saved in memory (Claim 13, Claim 27, contingent limitation not needed as they are if clauses)
A person of ordinary skill in the art would combine Bolger et al. with Martin et al. with Turner with Chen et al. with the addition of Schubert et al. because AdapterRemoval v2 because it adds barcode demultiplexing and quality aware read merging. All works are in the same field of computational methods for processing and handling sequence data and specifically removing adapter sequences. Each piece supplies a complementary part of a routine workflow. Martin teaches iteratively searching and removing adapters using a fixed portion of the adapter as a search. Bolger teaches seed based adapter detection within a defined series of overlapped positions. Turner teaches when the insert length is known the adapter begins at the next immediate base pair. There is a reasonable expectation of success as each step of the method works independently therefore, they are expected to work together. These are well understood methods of processing data, each method works independently so they are expected to and a person of ordinary skill in the art would understand how to combine the different methods to achieve the results.
Conclusion
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/C.H.B./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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