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  • Laros Laros j.f.j.laros
  • Mihai Lefter Mihai Lefter mlefter
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4 authors
  1. Oct 13, 2015
  3. Sep 23, 2015
    • Vermaat's avatar
      Show diff for variant protein from non-reference start codon · 3c98a1af
      Vermaat authored 
      The alternative variant protein sequence translated from a
non-reference start codon (created by the variant), was not
color-diffed as normal variant protein sequences are.

In the process we also rename the `oldprotein` and `newprotein`
fields in the output object to `oldProtein` and `newProtein` to
be more consistent with other field names.
      3c98a1af
    • Vermaat's avatar
      Visualise protein change, also with alternative start · 851e71fe
      Vermaat authored 
      In the case of an alternative start codon (in the reference CDS),
protein changes were not visualised. This is fixed and a WALTSTART
warning is also issued.

Also, if a new non-reference start codon is created by the variant,
visualise this as such.
      851e71fe
    • Vermaat's avatar
      Translate alternative start to M, also in variant · ae70ddfd
      Vermaat authored 
      In case of an alternative start codon, the variant CDS was not
translated to a protein starting with M. This caused the protein
description machinery to conclude a variant affecting the start
codon, hence reporting `p.?`.

We fix this by always translating the start codon to M (except
when the variant actually affects it).

Example: `NM_024426.4:c.1107A>G` (a synomymous mutation) should
yield `NM_024426.4(WT1_i001):p.(=)`, not `p.?`. The start codon
for that protein is `CTG`.
      ae70ddfd
  5. Aug 04, 2015
  7. Jul 15, 2015
    • Vermaat's avatar
      Uncertain stop codon in protein descriptions (fs and ext) · d2f91690
      Vermaat authored 
      When a variant results in a frame shift or extension and we don't
see a new stop codon in the RNA, the protein description should use
the notation for an uncertain stop codon, e.g., `p.(Gln730Profs*?)`
instead of `p.(Gln730Profs*96)` where 96 is just the last codon in
our transcript [1].

To detect this, we now use `to_stop=False` in our `.translate()`
calls, since that will explicitely return `*` characters for stop
codons.

We also slightly fix the coloring of changes in the protein sequence
where previously changed stop codon characters where not included.

[1] http://www.hgvs.org/mutnomen/FAQ.html#nostop
      d2f91690
  9. Jul 09, 2015
  11. Jan 30, 2015
  13. Oct 20, 2014
    • Vermaat's avatar
      Use unicode strings · 2a4dc3c1
      Vermaat authored 
      Don't fix what ain't broken. Unfortunately, string handling in Mutalyzer
really is broken. So we fix it.

Internally, all strings should be represented by unicode strings as much as
possible. The main exception are large reference sequence strings. These can
often better be BioPython sequence objects, since that is how we usually get
them in the first place.

These changes will hopefully make Mutalyzer more reliable in working with
incoming data. As a bonus, they're a first (small) step towards Python 3
compatibility [1].

Our strategy is as follows:

1. We use `from __future__ import unicode_literals` at the top of every file.
2. All incoming strings are decoded to unicode (if necessary) as soon as
   possible.
3. Outgoing strings are encoded to UTF8 (if necessary) as late as possible.
4. BioPython sequence objects can be based on byte strings as well as unicode
   strings.
5. In the database, everything is UTF8.
6. We worry about uploaded and downloaded reference files and batch jobs in a
   later commit.

Point 1 will ensure that all string literals in our source code will be
unicode strings [2].

As for point 4, sometimes this may even change under our eyes (e.g., calling
`.reverse_complement()` will change it to a byte string). We don't care as
long as they're BioPython objects, only when we get the sequence out we must
have it as unicode string. Their contents are always in the ASCII range
anyway.

Although `Bio.Seq.reverse_complement` works fine on Python byte strings (and
we used to rely on that), it crashes on a Python unicode string. So we take
care to only use it on BioPython sequence objects and wrote our own reverse
complement function for unicode strings (`mutalyzer.util.reverse_complement`).

As for point 5, SQLAlchemy already does a very good job at presenting decoding
from and encoding to UTF8 for us.

The Spyne documentation has the following to say about their `String` and
`Unicode` types [3]:

> There are two string types in Spyne: `spyne.model.primitive.Unicode` and
> `spyne.model.primitive.String` whose native types are `unicode` and `str`
> respectively.
>
> Unlike the Python `str`, the Spyne `String` is not for arbitrary byte
> streams. You should not use it unless you are absolutely, positively sure
> that you need to deal with text data with an unknown encoding. In all other
> cases, you should just use the `Unicode` type. They actually look the same
> from outside, this distinction is made just to properly deal with the quirks
> surrounding Python-2's `unicode` type.
>
> Remember that you have the `ByteArray` and `File` types at your disposal
> when you need to deal with arbitrary byte streams.
>
> The `String` type will be just an alias for `Unicode` once Spyne gets ported
> to Python 3. It might even be deprecated and removed in the future, so make
> sure you are using either `Unicode` or `ByteArray` in your interface
> definitions.

So let's not ignore that and never use `String` anymore in our webservice
interface.

For the command line interface it's a bit more complicated, since there seems
to be no reliable way to get the encoding of command line arguments. We use
`sys.stdin.encoding` as a best guess.

For us to interpret a sequence of bytes as text, it's key to be aware of their
encoding. Once decoded, a text string can be safely used without having to
worry about bytes. Without unicode we're nothing, and nothing will help
us. Maybe we're lying, then you better not stay. But we could be safer, just
for one day. Oh-oh-oh-ohh, oh-oh-oh-ohh, just for one day.

[1] https://docs.python.org/2.7/howto/pyporting.html
[2] http://python-future.org/unicode_literals.html
[3] http://spyne.io/docs/2.10/manual/03_types.html#strings
      2a4dc3c1
  15. Aug 27, 2014
  17. Mar 01, 2014
    • Vermaat's avatar
      Reverse complement range insertions/insertion-deletions · 57120a89
      Vermaat authored 
      The name checker supports reverse complement ranges in insertions
and insertions-deletions, for example `3_4ins8_12inv'.

Reverse complement range insertions and insertion-deletions are not
part of the current HGVS nomenclature, but will be proposed.
      57120a89
  19. Feb 28, 2014
    • Vermaat's avatar
      Range and compound insertions/insertion-deletions · 31b2f13a
      Vermaat authored 
      The name checker supports ranges in insertions and insertion-
deletions, for example `3_4ins8_12`, and compound insertions and
insertion-deletions, for example `3_4ins[ATC;8_12]`.
The inserted sequences are accepted and concatenated before any
further processing, so reported descriptions show only the
concatenated sequences.
The support for ranges is limited to genomic descriptions.

The position converter supports compound insertions and
insertion-deletions, not ranges.

Compound insertions and insertion-deletions are not part of the
current HGVS nomenclature, but will be proposed.
      31b2f13a
  21. Jan 22, 2014
    • Vermaat's avatar
      Use fixtures in the unit tests · c49d49f0
      Vermaat authored 
      This is The Good Stuff. The entire test suite can now be run without
having to setup a database, running the batch checker, any of the web
services or the website. It even passes without an internet connection.
In, like, 30 seconds! Awesome!

This means tests don't randomly fail after some reference sequence
changes on the NCBI server and it doesn't take an entire configured
server with mapping database setup to run the tests. Those are things
of the past! No more frustrations, Mutalyzer is testable!

Going down now...

The mountain screamed three times today
I guess it thought it'd like to play
How much does one have to pay
To fry a peak and melt away
Launching titan's breath on mine
The sweating measure lands on time

And the old man, down by the river
Well he walks up and he walks on down
To the spaceship that's parked at your doorstep
And it's waiting to take you away now

Goin' down now
Goin' down now

Looking for the rate that crowed
He's hooked up down in Mexico
Slap my nerve now give me more
It's my disaster friend, not yours

And the old man, down by the river
Well he walks up and he walks on down
To the spaceship that's parked at your doorstep
And it's waiting to take you away now

And the last one, it's down by the river
Where he gets up and he walks on down
To the spaceship that's parked at your doorstep
And it's waiting to take you away now

It's down by the river, it's always this way now
It's down by the river, it's always this way now

Going down now
Going down now
now, now, now

down, down, down
      c49d49f0
  23. Jan 04, 2014
  25. Dec 23, 2013
    • Vermaat's avatar
      Fix unit tests with SQLAlchemy · 94df7c07
      Vermaat authored 
      This involves making the SQLAlchemy session reconfigurable at run-time,
which is done automatically on updating the Mutalyzer configuration using
configuration update callbacks.
      94df7c07
  27. Dec 19, 2013
  29. Feb 25, 2013
  31. Feb 12, 2013
  33. Dec 11, 2012
  35. Oct 04, 2012
  37. Jul 26, 2012
  39. Jun 21, 2012
  41. Mar 12, 2012
  43. Feb 21, 2012
  45. Jan 31, 2012
  47. Jan 26, 2012
  49. Jan 25, 2012
  51. Dec 14, 2011
  53. Nov 24, 2011
  55. Nov 14, 2011
  57. Nov 08, 2011
  59. Nov 04, 2011
  61. Oct 20, 2011
  63. Aug 24, 2011
  65. Aug 18, 2011