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8 changes: 5 additions & 3 deletions mkdocs.yml
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pages:
- Introduction: 'index.md'
- User Guide:
- 'Installation': 'user-guide/installation.md'
- 'Output files': 'user-guide/output-files.md'
- 'License': 'license.md'
- Installation: 'user-guide/installation.md'
- Output files: 'user-guide/output-files.md'
- Note on recalibration: 'user-guide/recal.md'
- License: 'license.md'
- Software License Agreement: 'agreement.md'
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SOFTWARE LICENSE AGREEMENT (hereinafter referred to as AGREEMENT)
=================================================================

This is a legal agreement between you (hereinafter referred to as the LICENSEE)
and the University of Zurich, Rämistrasse 71, 8006 Zurich (hereinafter referred
to as UNIVERSITY OF ZURICH) pertaining to the right to use the software product
“MinVar” (hereinafter referred to as SOFTWARE). Using the SOFTWARE indicates
your acceptance of these terms and conclusion of the Agreement between the
LICENSEE and UNIVERSITY OF ZURICH.

1. Introduction
---------------

1.1 UNIVERSITY OF ZURICH Institute of Medical Virology, Dr. Osvaldo Zagordi
(PRINCIPAL INVESTIGATOR) has developed the SOFTWARE.

1.2 LICENSEE wishes to obtain a non-exclusive, non-transferable and
royalty-free license of the SOFTWARE for internal non-commercial research
purposes as specified in this AGREEMENT.

2. Grant/Scope of License
-------------------------

2.1 UNIVERSITY OF ZURICH hereby grants to LICENSEE a non-exclusive,
non-transferable, royalty-free license to use the SOFTWARE and any related
documentation for internal non-commercial research purposes. Commercial use of
the SOFTWARE requires a separately executed written license agreement.

2.2 UNIVERSITY OF ZURICH will not provide any services or support in connection
with the SOFTWARE or technical support within the scope of this AGREEMENT.

3. Permitted Use and Restrictions
---------------------------------

3.1 The license granted herein is for the internal non-commercial research
purposes of LICENSEE only.

3.2 LICENSEE may not duplicate or use the SOFTWARE or its contents to
manufacture or provide products, services or technologies (or portions thereof)
either directly or indirectly for commercialization or for any other direct or
indirect for-profit purposes.

3.3 LICENSEE agrees to reference the publication:

_Huber et al._, MinVar: A rapid and versatile tool for HIV-1 drug resistance
genotyping by deep sequencing
Journal of Virological Methods, Volume 240, February 2017, Pages 7-13
https://doi.org/10.1016/j.jviromet.2016.11.008

in any publications reporting use of it or any manual or document.
The LICENSEE is asked to forward to the PRINCIPAL INVESTIGATOR a copy of all
reports and papers that are for public or general release that use the
SOFTWARE.

4. Warranty Disclaimer
----------------------

4.1 THE LICENSED SOFTWARE IS PROVIDED "AS IS" AND UNIVERSITY OF ZURICH MAKES NO
REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED. BY WAY OF EXAMPLE, BUT
WITHOUT LIMITATION, UNIVERSITY OF ZURICH MAKES NO REPRESENTATIONS OR WARRANTIES
OF MERCHANTABILITY OR FITNESS FOR ANY PARTICULAR PURPOSE OR THAT THE FUNCTIONS
CONTAINED IN THE SOFTWARE WILL MEET LICENSEE'S REQUIREMENTS OR THAT THE USE OF
THE LICENSED SOFTWARE OR DOCUMENTATION WILL NOT INFRINGE ANY THIRD PARTY'S
PATENTS, COPYRIGHTS, TRADEMARKS OR OTHER RIGHTS. FURTHERMORE, UNIVERSITY OF
ZURICH DOES NOT WARRANT OR MAKE ANY REPRESENTATIONS REGARDING THE USE OR THE
RESULTS OF THE USE OF THE SOFTWARE IN TERMS OF CORRECTNESS, ACCURACY,
RELIABILITY, OR OTHERWISE OR THAT DEFECTS IN THE SOFTWARE WILL BE CORRECTED.
UNIVERSITY OF ZURICH WILL NOT BE LIABLE FOR ANY CONSEQUENTIAL, INCIDENTAL, OR
SPECIAL DAMAGES, OR ANY OTHER RELIEF, OR FOR ANY CLAIM BY ANY THIRD PARTY,
ARISING FROM THE USE OF THE LICENSED SOFTWARE.

4.2 The LICENSEE expressly acknowledges and agrees that the use of the SOFTWARE
is at LICENSEE's sole risk and to hold harmless and indemnify UNIVERSITY OF
ZURICH, and its affiliates, employees or partners, from and against any third
party claim arising from or in any way related to LI-CENSEE's use of SOFTWARE,
violation of this AGREEMENT or any other actions in connection with the use of
SOFTWARE.

5. Title and Ownership
----------------------

Title, ownership rights, and intellectual property rights in and to the
SOFTWARE shall remain with UNIVERSITY OF ZURICH.

6. Term and Termination
-----------------------

6.1 This AGREEMENT shall become effective upon download of the SOFTWARE by
LICENSEE.

6.2 UNIVERSITY OF ZURICH may terminate this AGREEMENT upon 30 (thirty) days
advance written e-mail notification to LICENSEE. Upon evidence of violation of
any of the terms under this AGREEMENT by LICENSEE, UNIVERSITY OF ZURICH may
terminate this AGREEMENT without previous notice.

6.3 Upon termination LICENSEE is obliged to uninstall the SOFTWARE from all its
computers and to destroy any copies of the SOFTWARE kept according to this
AGREEMENT.

6.4 Unless earlier terminated, this AGREEMENT shall automatically expire at the
end of two years after download of the SOFTWARE by LICENSEE.

6.5 Articles 4 and 5 shall survive the termination or expiration of this
AGREEMENT for any reason in addition to those articles surviving by operation
of law.

7. Miscellaneous
----------------

7.1 This AGREEMENT and the license granted herein or any part thereof under
this AGREEMENT are not assignable by LICENSEE without the prior written
approval of UNIVERSITY OF ZURICH.

7.2 LICENSEE shall not use the names or trademarks of UNIVERSITY OF ZURICH, its
related entities and its employees, or any adaptations thereof, in any
advertising, promotional or sales literature, or in any securities reports
required by the respective authorities, without the prior written consent of
the UNIVERSITY OF ZURICH.

7.3 Each party is acting as an independent contractor and not as an agent,
partner, or joint venture with the other party for any purpose. Neither party
shall have any right, power or authority to act or create any obligation,
express or implied, on behalf of the other.

7.4 This AGREEMENT sets forth the entire AGREEMENT between the parties with
respect to the subject matter hereof. No supplement, modification or amendment
of this AGREEMENT shall be binding, unless in writing signed by a duly
authorized representative of each party to the AGREEMENT.

7.5 Should some or several provisions of this AGREEMENT be ineffective or
invalid, or should there be an omission in this AGREEMENT, the effectiveness,
respectively the validity of the remaining provisions shall not be affected
thereby. An ineffective, respectively, invalid provision shall be replaced by
the interpretation of the agreement which comes nearest to the economic meaning
and the envisaged economic purpose of the ineffective respectively, invalid
provision. The same applies in the case of a contractual gap

7.6 The terms stipulated in this AGREEMENT may not be modified in any way
without the mutual consent of the parties in writing.

8. Governing Law and Jurisdiction
---------------------------------

THIS AGREEMENT SHALL BE GOVERNED BY THE LAWS OF SWITZERLAND. Any dispute
arising from or in connection with this AGREEMENT will be finally settled by
the courts of Zurich, Switzerland.
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# License

MinVar relies on some third-party tools with their own specific licenses.
It is worthy of note that recalibration is done by GATK, which is itself
MinVar is licensed for free for non-commercial purposes according to
[this agreement](agreement.md). Its commercial use requires a separately
executed written license agreement, please
[contact us](https://ozagordi.github.io/MinVar/#contact).

MinVar relies on the following libraries with their own specific licenses:

- pandas (library for data analysis) [simplified BSD licence](http://pandas.pydata.org/pandas-docs/stable/overview.html#license)
- Biopython (library for biological computation), distributed under [Biopython licence](https://github.com/biopython/biopython/blob/master/LICENSE.rst)

The following external tools are called by the program:

- BLAST (sequence alignment), code distributed in lesser GPL
- samtools (sequence manipulation), [MIT licence](https://github.com/samtools/samtools/blob/develop/LICENSE)
- GATK (base quality recalibration), commercial licence (see below)
- picard-tools (sequence manipulation), only used together with GATK, [MIT licence](https://github.com/broadinstitute/picard/blob/master/LICENSE.txt)
- bwa (sequence alignment), [GPL v3 licence](https://github.com/lh3/bwa/blob/master/COPYING)
- seqtk (sequence filtering), [MIT licence](https://github.com/lh3/seqtk/blob/master/LICENSE)
- lofreq (variant calling), [MIT licence](https://github.com/CSB5/lofreq/blob/master/LICENSE)

### Using recalibration in a commercial setting

It is worth noting that recalibration is done by GATK, which is itself
subject to a dual purpose [licensing](https://software.broadinstitute.org/gatk/download/licensing.php):
free for academic non-commercial research activities, subject to a fee for commercial use.

While you are free to use MinVar without restriction for research purposes, its
commercial licensing is under definition.
Starting from v1.2, MinVar by defaults does not recalibrate the base quality
scores (you can evaluate the difference in this
[Note on recalibration](user-guide/recal.md)). If you decide to use MinVar
with recalibration for commercial purposes, you will have to obtain a licence
for GATK from Broad Institute.
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# Effect of recalibration

MinVar can call GATK BaseRecalibrator to adjust quality scores. Up to version
1.1 this option was on by default, from version 1.2 this has changed.
While GATK is free for non-commercial purposes, a licence must be acquired from
Broad Institute (creator of GATK) if one uses it for profit.

In order to support users in deciding whether to buy GATK licence or not,
this page displays a comparison of mutations detected with and without base
quality scores recalibration.

The following scatterplots report the frequencies of amino acid mutations in the
mixes used in the [MinVar paper](http://dx.doi.org/10.1016/j.jviromet.2016.11.008)
both with and without recalibration performed with GATK BaseRecalibrator. The
colours indicate whether the mutation was expected or not (_i.e._, present in
the original virus stocks), while the shape indicates the gene where it is
found (protease or reverse transcriptase).

The names of the mixes indicate different mixing proportions of viral stocks
and viral titers (100,000 and 10,000 copies/mL). See the paper and the file
`viral_mixes.md` in the [data repository](https://zenodo.org/record/44921) on Zenodo.


## Geometric mix (51.6%, 25.8%, 12.9%, 6.5%, and 3.2%)

![Geometric mix: 1E4 viral load](./images/scatter_plot_mix_GEO_1E4.pdf "Geometric mix 1E4")

![Geometric mix: 1E5 viral load](./images/scatter_plot_mix_GEO_1E5.pdf "Geometric mix 1E5")

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