Bioinformatics Patents on Burrows Wheeler Transform

Bioinformatics Patents on Burrows Wheeler Transform

While “Complete Genomics, Illumina Settle Patent Infringement Lawsuits”, bioinformaticians will be looking forward to a new level of nuisance.

Pacbio’s BLASR patent:


United States Patent Application 20120330566 Kind Code: A1


Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof. In particularly preferred embodiments, nucleic acid sequences generated by such methods are subjected to de novo assembly and/or consensus sequence determination.

Inventor: Chaisson, Mark (San Francisco, CA, US)

Assignee: Pacific Biosciences of California, Inc. (Menlo Park, CA, US)

Does that mean anyone using BLASR is violating the patent? Or anyone implementing an alignment algorithm with the following rules?

A method of aligning a sequence read to a reference sequence, comprising: a) sequencing a target nucleic acid to provide a sequence read; b) providing a reference sequence for the target nucleic acid; c) finding a set of subsequences in the sequence read that match portions of the reference sequence; d) refining the set of subsequences, wherein the refining comprises scoring and realigning the subsequences using sparse dynamic programming; and e) scoring and realigning a final set of subsequences using a banded alignment, thereby aligning the sequence read to the reference sequence.

2. The method of claim 1, wherein the finding comprises finding all exact matches from the sequence read that are longer than a minimum match length k and that match the reference sequence.

3. The method of claim 2, wherein k is between 8 and 15.


BWA-MEM chains the seeds during the alignment. Does that mean use of BWA-MEM in GATK violates PacBio patents?

5. The method of claim 1, wherein the finding comprises clustering exact matches using global chaining.


15. The method of claim 1, wherein the sequencing is performed using a method selected from the group consisting of pyrosequencing, tSMS sequencing, Sanger sequencing, Solexa sequencing, SMRT sequencing, SOLiD sequencing, Maxam and Gilbert sequencing, nanopore sequencing, and semiconductor sequencing.


Illumina’s BCR patent (applied, not granted):


The present disclosure provides computer implemented methods and systems for analyzing datasets, such as large data sets output from nucleic acid sequenceing technologies. In particular, the present disclosure provides for data analysis comprising computing the BWT of a collection of strings in an incremental, character by character, manner. The present disclosure also provides compression boosting strategies resulting in a BWT of a reordered collection of data that is more compressible by second stage compression methods compared to non-reordered computational analysis.

United States Patent Application 20120330567 Kind Code: A1


Bauer, Markus J. (Mariapfarr, AT)

Cox, Anthony James (Nr Saffron Walden, GB)

Rosone, Giovanna (Palermo, IT)

Evers, Dirk (Arkesden, GB)

Assignee: ILLUMINA CAMBRIDGE LIMITED (Nr Saffron Walden, GB)

Hmm…seems like Jared Simpson’s string graph assembler cannot be used any more given that its index creation violates this patent (Please see an update from Jared at the bottom).

1. A method for determining the sequence of a nucleic acid comprising: a) receiving a collection of data strings from a nucleic acid sequence dataset wherein said data strings comprise a plurality of characters, b) generating a Burrows Wheeler transform on a first collection of characters, wherein the first collection of characters comprises a first character from each of said data strings, c) merging a second collection of characters with said first collection of characters to form a merged collection of characters, wherein the second collection of characters comprises a second character from each of said data strings, d) augmenting the Burrows Wheeler transform from the merged first and second collection of characters, and e) determining the sequence of the nucleic acid based on the Burrows Wheeler transform of the nucleic acid.



Unrelated alignment-related patents (does not use BWT)

V. Galinsky claiming to do better than Smith-Waterman.

Method for rapid assessment of similarity between sequences - V. Galinsky

Method for fast and accurate alignment of sequences - V. Galinsky

Application number: 20130041593

Abstract: Genomic sequence matching and alignment techniques are disclosed. In one embodiment of the invention, computerized methods are provided for analyzing sequence similarity data obtained by means of a table of all local hits recorded between query sequence and reference index. The table of local hits represents all occurrences of query subsequences in reference index that stored all transitions between single l-mer prefix to multiple m-mer suffixes. The index data structure may take a variety of forms, including an array or a tree. The base position of each transition from l-prefix to m-suffix is recorded in k-bit masked form. The positions data structure may take a variety of forms as well, including an array or a tree. The table of local hits derived from l-prefix, m-suffix and k-position reference index is used by a series of low time and space complexity algorithms for optimizing alignment between query and reference.

Gimme a break !!! Can you patent something in GPU and FPGA without implementing anything in GPU and FPGA? In the earlier days, people claiming to build better mousetrap had to build one before patenting.

Of course the above patents are irrelevant, because

Forget Gene Patents. Co-founder of 23andMe Patents Personalized Genomics



An Update from Jared Simpson regarding SGA

We contacted Jared Simpson, Heng Li and Anthony Cox about the implications of above patents.

Anthony Cox corrected us about the status of the patent. Currently, their innovation on BCR is under pending status under review and not a granted patent. Also, he highlighted our previous discussion in the BEETL/ISAAC thread, where he explained IP position of Illumina in the comment section.

“My understanding of the license is that it is meant to allow you to do pretty much whatever you want with the code install, use, distribute, modify for non- commercial purposes.”

Academic Bioinformaticians Uncomfortable with Illuminas Publication of Variant Caller

Jared wrote back to us:

We are aware of Illumina’s patent and discussed our implementation of BCR with them. They agreed that we can release our implementation as long as we provided a notice in SGA’s README ( I was satisfied with this arrangement but am generally opposed to algorithm patents.

Does that clear up SGA? We doubt it until Illumina lawyers write something up explaining what they agree to and what they do not.

i) Can SGA be used for commercial and non-commercial purposes? (To save readers time, we had a similar discussion with Tony Cox earlier on another program recently released by Illumina - Academic Bioinformaticians Uncomfortable with Illuminas Publication of Variant Caller).

ii) Can SGA, a GPL-licensed code, be modified and ‘sold’ by anyone other than Jared, provided he follows GPL’s rules about releasing the source code? Or does each programmer have to separately negotiate with Illumina’s IP office to get the same approval that Jared got?

iii) If SGA can be updated by anyone other than Jared, can that person turn off all other blocks of SGA and keep only the BCR-inspired library, but still call the forked version SGA? What is the patent protecting then?

Oh well, we should not have mentioned (iii) before seeing the signed document regarding (i) and (ii) :)

Written by M. //