From fc872f15da426926414fb7629bf6660d9880ed1e Mon Sep 17 00:00:00 2001
From: Pjotr Prins
Date: Fri, 10 Apr 2020 17:16:35 -0500
Subject: Draft

---
 paper/paper.md | 160 ++++++++++++++++++++++++++++++++++++++++++++++++---------
 1 file changed, 135 insertions(+), 25 deletions(-)

(limited to 'paper/paper.md')

diff --git a/paper/paper.md b/paper/paper.md
index caa9903..813c91b 100644
--- a/paper/paper.md
+++ b/paper/paper.md
@@ -1,8 +1,9 @@
 ---
-title: 'Public Sequence Resource for COVID-19'
+title: 'CPSR: COVID-19 Public Sequence Resource'
+title_short: 'CPSR: COVID-19 Public Sequence Resource'
 tags:
   - Sequencing
-  - COVID
+  - COVID-19
 authors:
   - name: Pjotr Prins
     orcid: 0000-0002-8021-9162
@@ -25,16 +26,30 @@ authors:
   - name: Rutger Vos
     orcid: 0000
     affiliation: 7
-  - Michael Heuer
+  - name: Michael Heuer
     orcid: 0000
     affiliation: 8
-
+  - name: Adam Novak
+    orcid: 0000
+    affiliation: 9
+  - name: Alex Kanitz
+    orcid: 0000
+    affiliation: 10
+  - name: Jerven Bolleman
+    orcid: 0000
+    affiliation: 11
+  - name: Joep de Ligt
+    orcid: 0000
+    affiliation: 12
 affiliations:
   - name: Department of Genetics, Genomics and Informatics, The University of Tennessee Health Science Center, Memphis, TN, USA.
     index: 1
   - name: Curii, Boston, USA
     index: 2
 date: 11 April 2020
+event: COVID2020
+group: Public Sequence Uploader
+authors_short: Pjotr Prins & Peter Amstutz \emph{et al.}
 bibliography: paper.bib
 ---
 
@@ -49,13 +64,48 @@ pasting above link (or yours) with
 
   https://github.com/biohackrxiv/bhxiv-gen-pdf
 
+Note that author order will change!
+
 -->
 
 # Introduction
 
-As part of the one week COVID-19 Biohackathion 2020, we formed a
-working group on creating a public sequence resource for Corona virus.
-
+As part of the COVID-19 Biohackathion 2020 we formed a working
+group to create a COVID-19 Public Sequence Resource (CPSR) for
+Corona virus sequences. The general idea was to create a
+repository that has a low barrier to entry for uploading sequence
+data using best practices. I.e., data published with a creative
+commons 4.0 (CC-4.0) license with metadata using state-of-the art
+standards and, perhaps most importantly, providing standardized
+workflows that get triggered on upload, so that results are
+immediately available in standardized data formats.
+
+Existing data repositories for viral data include GISAID, EBI ENA
+and NCBI. These repositories allow for free sharing of data, but
+do not add value in terms of running immediate
+computations. Also, GISAID, at this point, has the most complete
+collection of genetic sequence data of influenza viruses and
+related clinical and epidemiological data through its
+database. But, due to a restricted license, data submitted to
+GISAID can not be used for online web services and on-the-fly
+computation. In addition GISAID registration which can take weeks
+and, painfully, forces users to download sequences one at a time
+to do any type of analysis. In our opinion this does not fit a
+pandemic scenario where fast turnaround times are key and data
+analysis has to be agile.
+
+We managed to create a useful sequence uploader utility within
+one week by leveraging existing technologies, such as the Arvados
+Cloud platform [@Arvados], the Common Workflow Langauge (CWL)
+[@CWL], Docker images built with Debian packages, and the many
+free and open source software packages that are available for
+bioinformatics.
+
+The source code for the CLI uploader and web uploader can be
+found [here](https://github.com/arvados/bh20-seq-resource)
+(FIXME: we'll have a full page). The CWL workflow definitions can
+be found [here](https://github.com/hpobio-lab/viral-analysis) and
+on CWL hub (FIXME).
 
 <!--
 
@@ -73,38 +123,98 @@ working group on creating a public sequence resource for Corona virus.
 
 ## Cloud computing backend
 
-Peter, Pjotr, MichaelC
-
-## A command-line sequence uploader
+The development of CPSR was accelerated by using the Arvados
+Cloud platform. Arvados is an open source platform for managing,
+processing, and sharing genomic and other large scientific and
+biomedical data. The Arvados instance was deployed on Amazon AWS
+for testing and development and a project was created that
+allows for uploading data.
 
-Peter, Pjotr
+## Sequence uploader
 
-## Metadata uploader
+We wrote a Python-based uploader that authenticates with Arvados
+using a token. Data gets validated for being a FASTA sequence,
+FASTQ raw data and/or metadata in the form of JSON LD that gets
+validated against a schema. The uploader can be used
+from a command line or using a simple web interface.
 
-With Thomas
+## Creating a Pangenome
 
-## FASTA to GFA workflow
+### FASTA to GFA workflow
 
-Michael Heuer
+The first workflow (1) we implemented was a FASTA to Graphical
+Fragment Assembly (GFA) Format conversion. When someone uploads a
+sequence in FASTA format it gets combined with all known viral
+sequences in our storage to generate a pangenome or variation
+graph (VG). The full pangenome is made available as a
+downloadable GFA file together with a visualisation (Figure 1).
 
-## BAM to GFA workflow
+### FASTQ to GFA workflow
 
-Tazro & Erik
+In the next step we introduced a workflow (2) that takes raw
+sequence data in fastq format and converts that into FASTA.
+This FASTA file, in turn, gets fed to workflow (1) to generate
+the pangenome.
 
-## Phylogeny app
+## Creating linked data workflow
 
-With Rutger
+We created a workflow (3) that takes GFA and turns that into
+RDF. Together with the metadata at upload time a single RDF
+resource is compiled that can be linked against external
+resources such as Uniprot and Wikidata. The generated RDF file
+can be hosted in any triple store and queried using SPARQL.
 
-## RDF app
+## Creating a Phylogeny workflow
 
-Jerven?
+WIP
 
-## EBI app
-
-?
+## Other workflows?
 
 # Discussion
 
-Future work...
+CPSR is a data repository with computational pipelines that will
+persist during pandemics.  Unlike other data repositories for
+Sars-COV-2 we created a repository that immediately computes the
+pangenome of all available data and presents that in useful
+formats for futher analysis, including visualisations, GFA and
+RDF. Code and data are available and written using best practises
+and state-of-the-art standards. CPSR can be deployed by anyone,
+anywhere.
+
+CPSR is designed to abide by FAIR data principles (expand...)
+
+CPSR is primed with viral data coming from repositories that have
+no sharing restrictions. The metadata includes relevant
+attribution to uploaders. Some institutes have already committed
+to uploading their data to CPSR first so as to warrant sharing
+for computation.
+
+CPSR is currently running on an Arvados cluster in the cloud. To
+ascertain the service remains running we will source money from
+project during pandemics. The workflows are written in CWL which
+means they can be deployed on any infrastructure that runs
+CWL. One of the advantages of the CC-4.0 license is that we make
+available all uploaded sequence and meta data, as well as
+results, online to anyone. So the data can be mirrored by any
+party. This guarantees the data will live on.
+
+<!-- Future work... -->
+
+We aim to add more workflows to CPSR, for example to prepare
+sequence data for submitting in other public repositories, such
+as EBI ENA and GISAID. This will allow researchers to share data
+in multiple systems without pain, circumventing current sharing
+restrictions.
+
+# Acknowledgements
+
+We thank the COVID-19 BioHackathon 2020 and ELIXIR for creating a
+unique event that triggered many collaborations. We thank Curii
+Corporation for their financial support for creating and running
+Arvados instances.  We thank Amazon AWS for their financial
+support to run COVID-19 workflows. We also want to thank the
+other working groups in the BioHackathon who generously
+contributed onthologies, workflows and software.
+
 
 # References
-- 
cgit v1.2.3


From dcd7f12d10e7f6399a0d515606148f85358d9dc7 Mon Sep 17 00:00:00 2001
From: Michael L Heuer
Date: Fri, 10 Apr 2020 17:52:45 -0500
Subject: Add author and affiliation

---
 paper/paper.md | 4 +++-
 1 file changed, 3 insertions(+), 1 deletion(-)

(limited to 'paper/paper.md')

diff --git a/paper/paper.md b/paper/paper.md
index 813c91b..bc7e835 100644
--- a/paper/paper.md
+++ b/paper/paper.md
@@ -27,7 +27,7 @@ authors:
     orcid: 0000
     affiliation: 7
   - name: Michael Heuer
-    orcid: 0000
+    orcid: 0000-0002-9052-6000
     affiliation: 8
   - name: Adam Novak
     orcid: 0000
@@ -46,6 +46,8 @@ affiliations:
     index: 1
   - name: Curii, Boston, USA
     index: 2
+  - name: RISE Lab, University of California Berkeley, Berkeley, CA, USA.
+    index: 8
 date: 11 April 2020
 event: COVID2020
 group: Public Sequence Uploader
-- 
cgit v1.2.3


From 89f996912240cfb2f5adcf95f401dd59319dac3b Mon Sep 17 00:00:00 2001
From: Adam Novak
Date: Fri, 10 Apr 2020 16:28:08 -0700
Subject: Add affiliation info

---
 paper/paper.md | 6 ++++--
 1 file changed, 4 insertions(+), 2 deletions(-)

(limited to 'paper/paper.md')

diff --git a/paper/paper.md b/paper/paper.md
index 813c91b..b789f60 100644
--- a/paper/paper.md
+++ b/paper/paper.md
@@ -29,8 +29,8 @@ authors:
   - name: Michael Heuer
     orcid: 0000
     affiliation: 8
-  - name: Adam Novak
-    orcid: 0000
+  - name: Adam M Novak
+    orcid: 0000-0001-5828-047X
     affiliation: 9
   - name: Alex Kanitz
     orcid: 0000
@@ -46,6 +46,8 @@ affiliations:
     index: 1
   - name: Curii, Boston, USA
     index: 2
+  - name: UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA 95064, USA.
+    index: 9
 date: 11 April 2020
 event: COVID2020
 group: Public Sequence Uploader
-- 
cgit v1.2.3


From fcd45e42942750950076553ac995d738c863aa7a Mon Sep 17 00:00:00 2001
From: Adam Novak
Date: Fri, 10 Apr 2020 16:30:21 -0700
Subject: Grab Erik

---
 paper/paper.md | 4 ++--
 1 file changed, 2 insertions(+), 2 deletions(-)

(limited to 'paper/paper.md')

diff --git a/paper/paper.md b/paper/paper.md
index b789f60..e7678dc 100644
--- a/paper/paper.md
+++ b/paper/paper.md
@@ -31,7 +31,7 @@ authors:
     affiliation: 8
   - name: Adam M Novak
     orcid: 0000-0001-5828-047X
-    affiliation: 9
+    affiliation: 5
   - name: Alex Kanitz
     orcid: 0000
     affiliation: 10
@@ -47,7 +47,7 @@ affiliations:
   - name: Curii, Boston, USA
     index: 2
   - name: UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA 95064, USA.
-    index: 9
+    index: 5
 date: 11 April 2020
 event: COVID2020
 group: Public Sequence Uploader
-- 
cgit v1.2.3