why Compression of DNA sequences is a very challenging task?

[omran farhat]

why the compression of DNA sequence is a difficult for compression algorithms?
although DNA is composed of four bases (A, T, G, C), and can be coded using two bits per base , The human genome contains around 3 billion characters .although these software are designed for text compression.

[Shelwien]

The problem is that even when its this kind of DNA data (and its not always this - the previous dna compression competition used a different encoding),
its not just random independent symbols which can be packed to 2 bits each and that's all - it can be compressed much further than that.
For one, there're some common strings which appear frequently enough, so plain LZ would compress it better than just 2-bit packed coding.
But then, there're lots of other types of dependencies which don't normally appear in data compression - like palindromes,
complementary strings, imprecise matches, and even some restrictions appearing from the molecular structure of DNA sequence.

So I'd say its hard mainly because you have to know a lot about its properties to compress it well.
Also some things like imprecise matches are just hard to do on their own.

[JamesB]

Several small things, but none of them insurmountable.

Firstly, DNA consists (mostly) of just 4 symbols, meaning that bit-based encoding like Huffman is just never going to beat 2 bits per base at raw entropy encoding and in practice doesn't get that far due to often having an EOF symbol. Trivial workaround is to pack multiple bases per byte - eg triplets (permitting ACGTN). Try gzip on a dna sequence and you'll see it's really weak due to the small alphabet penalties of its huffman implementation.

Secondly, if you want LZ style matching then DNA is comparable to a corrupted archive. You'll be able to deduplicate a lot, but there are various imperfect repeats too, sometimes not just substitutions but small insertions and deletions. While this could be coded as a whole series of separate exact repeats (eg lots of LZ matches), it's inefficient as the distances are highly correlated (so maybe you need to use a more complex LZ with recent distance codes). Alternatively you can do a full smith-waterman style dynamic programming matrix to identify the repeats and the optimal edits from one to the other, permitting a richer LZ scheme.

Then just to make life awkward, matches can occur on either strand (so AT<>TA and CG<>GC plus reverse order).

Imagine trying to describe the duplications in this sequence:

https://www.researchgate.net/figure/...ns-where-there

Each dot on that graph is a short match between substrings of a pair of DNA sequences, but it could equally be between a DNA sequence and itself (making it perfectly symmetrical along the leading diagonal). The dots combine to make lines where the matches are long, either matching the leading diagonal for forward strand match or at right angles for a reverse strand match. The small repeat many times over gives rise to an approximate grid of short matches, but they're not quite all identical.


Frankly though it's probably not worth doing anything clever. Basic LZ (albeit both strands) coupled with 2 bit encoding and an exception matrix for the non ACGT symbols would get you 99% of the way there I think.

PS. Using dot plots on other data can be a nice way to visualise the repeat structure. Even just turning data into DNA via 2-bit encoding and using dotter (or similar) can shine a light on the internal data structure.

[Jyrki Alakuijala]

why the compression of DNA sequence is a difficult for compression algorithms?

Because of mutations, length optimization by evolution, and sex (and other exchange of dna) the dna has increased entropy, and is difficult to compress.

Some 3–10th order context modeling seems to help a tiny bit. Non-scientific personal theory: I believe a longer context model works better than shorter because the protein coming from the synthesis would have a self-collision or collision with the machinery building proteins with some of the sequences, and could not be completed or would be much slower to be completed. Such protein synthesis would seem harmful for most life, and thus is less common.

[Matt Mahoney]

The best you can compress any string is to find the shortest program that outputs it. The program that wrote the human genome is called evolution. It is not a complex algorithm, but it required 10^48 DNA base copy operations on 10^38 bits of memory, consuming 280 terawatts of power for 3.5 billion years.

I hope that including the human genome as 30% of the 10 GB benchmark will spur research in genomics in the same way that the large text benchmark spurs research in AI.

[CompressMaster]

btw, lossy DNA compression are called "mutations" such as cystic fibrosis, epidermolysis bullosa (extreme skin fragility), progeria (extremely fast aging), cancer and so on. The only hope is gene editing tool CRISPR/Cas9. For example, one patient with EB was fully cured:

Recessive dystrophic epidermolysis bullosa, an aggressive subtype of epidermolysis bullosa, is a rare disease resulting in severe skin fragility, characterized by the continuous formation of erosions and blisters on the skin and internal mucous membranes, as well as fibrosis and diverse complications such as pseudo-syndactyly (fusion of the fingers) and an elevated risk of developing metastatic squamous cell carcinoma. Dealing with this disease represents a challenge for health professionals and a great effort on the part of patients and their families.

This disease, of a genetic origin, is caused by mutations in the COL7A1 gene, which codifies for type VII collagen (C7), a protein essential for dermo-epidermal adhesion.

Gene editing with CRISPR/Cas9

The authors of this study have applied the gene-editing tool CRISPR/Cas9, which in this case is employed to safely and accurately eliminate from the stem cells of the skin of patients the exon 80 of the COL7A1 gene, which contains the pathogenic mutation. This leads to the production, from the edited cells, of a functional C7 variant.

cystic fibrosis