With the change introduced by #65 we forgot if the variant RNA has an
alternative downstream stop codon and therefore always reported ext*?
when the original stop codon was removed.

Fixes #145

This fixes a bug where transcripts created from CDS by construction did
not show up in the legend because the legend was created before that
construction.

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.

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.

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`.

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

Many genbank reference files contain more than one gene, especially
slices from an assembly. Some of these genes may be incomplete in
the reference file (i.e., either start or end exceeds the outer
coordinates). We cannot really do anything with these genes, so we
discard them during parsing.

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

See http://pytest.org/

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.

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.

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

This involves making the SQLAlchemy session reconfigurable at run-time,
which is done automatically on updating the Mutalyzer configuration using
configuration update callbacks.

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@671 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@667 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/branches/lrg-schema-update@654 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@617 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@590 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@557 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@556 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@497 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

For UD slices we also generate g. descriptions on the chromosome reference. We
now also apply the roll rule there and use correct ranges and sequences on the
reverse strand. Fixes #75.


git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@495 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@488 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@472 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@470 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@452 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@445 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@435 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/branches/browser-link-branch@423 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@418 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

Fixes #74.


git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/trunk@410 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1

The old way of using the configuration file was by instantiating a Config
object which read the file. This instance was passed to every function and
object that might need it.

The new way is by simply calling config.get('name') to get the configuration
value for 'name'. This lazily reads the configuration file and the contents
are cached for future calls.


git-svn-id: https://humgenprojects.lumc.nl/svn/mutalyzer/branches/implicit-config-branch@408 eb6bd6ab-9ccd-42b9-aceb-e2899b4a52f1