Merge pull request #199 from TheJacksonLaboratory/release/v1.0.0-RC4

Release v1.0.0-RC4

.github/workflows/maven.yml

@@ -31,4 +31,4 @@ jobs:
           restore-keys: ${{ runner.os }}-m2
 
       - name: Build with Maven
-        run: mvn -B package --file pom.xml
+        run: mvn -B verify --file pom.xml

.gitignore

@@ -37,3 +37,7 @@ data/
 # Sphinx documentation
 docs/_build/
 /dependency-reduced-pom.xml
+
+### The empty SvAnna database meant to be used with IDE to provide autocompletion etc.
+1710_svanna_empty.mv.db
+1710_svanna_empty.trace.db

CHANGELOG.rst

@@ -2,6 +2,22 @@
 Changelog
 =========
 
+------
+latest
+------
+
+
+----------
+v1.0.0-RC4
+----------
+
+- Treat deletion and duplications that affect CDS but do not change the reading frame in a milder way. Daniel Danis 12/1/21, 3:37 PM
+- Drop the TAD idea and only evaluate the variant with respect to the overlapping genomic elements
+- Externalize gene model and gene definition sources
+- Report a track with dosage sensitive regions in the HTML report
+- Store gene/disease/phenotype mapping in the database instead of the files in the data directory
+- Improve logging - create a log file in the current working directory and store ``DEBUG`` info in the file
+
 ----------
 v1.0.0-RC3
 ----------

docs/conf.py

@@ -1,9 +1,9 @@
 # -*- coding: utf-8 -*-
 #
-# VPV documentation build configuration file, created by
+# SvAnna documentation build configuration file, created by
 # sphinx-quickstart on Sun Sep 24 12:02:05 2017.
 #
-# This file is execfile()d with the current directory set to its
+# This file is executed with the current directory set to its
 # containing dir.
 #
 # Note that not all possible configuration values are present in this
@@ -14,7 +14,7 @@
 
 # If extensions (or modules to document with autodoc) are in another directory,
 # add these directories to sys.path here. If the directory is relative to the
-# documentation root, use os.path.abspath to make it absolute, like shown here.
+# documentation root, use os.path.abspath() to make it absolute, like shown here.
 #
 # import os
 # import sys
@@ -56,7 +56,7 @@
 # The short X.Y version.
 version = u'1.0'
 # The full version, including alpha/beta/rc tags.
-release = u'1.0.0-RC3'
+release = u'1.0.0-RC4'
 
 # The language for content autogenerated by Sphinx. Refer to documentation
 # for a list of supported languages.
@@ -141,7 +141,7 @@
 # (source start file, target name, title,
 #  author, documentclass [howto, manual, or own class]).
 latex_documents = [
-    (master_doc, 'SvAnna.tex', u'svann Documentation',
+    (master_doc, 'SvAnna.tex', u'SvAnna Documentation',
      u'Daniel Danis, Peter N Robinson', 'manual'),
 ]
 

docs/examples.rst

@@ -0,0 +1,272 @@
+.. _rstexamples:
+
+========
+Examples
+========
+
+This section shows how SvAnna prioritizes various structural variant classes.
+The resulting HTML reports contain graphics that are reported in the supplement of SvAnna paper.
+
+The examples work with variants stored in `examples.vcf`_ file. The VCF file is stored in SvAnna GitHub repository.
+
+Single exon deletion
+^^^^^^^^^^^^^^^^^^^^
+
+A deletion of 6.93 kb (``chr17:31,150,798-31,157,725del``) affecting *NF1* that was assigned a *PSV* score of 157.95.
+
+The deletion affects exon 2 of several *NF1* transcripts.
+Pathogenic variants in *NF1* are associated with neurofibromatosis type 1 (``OMIM:162200``).
+
+The phenotypic features curated for the proband ``UAB-1`` were:
+
+* ``HP:0007565`` Multiple cafe-au-lait spots
+* ``HP:0009732`` Plexiform neurofibroma
+* ``HP:0009735`` Spinal neurofibromas
+* ``HP:0009736`` Tibial pseudarthrosis
+
+Data were curated from a published case report in `Decoding NF1 Intragenic Copy-Number Variations`_.
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0007565 --term HP:0009732 --term HP:0009735 --term HP:0009736
+
+
+
+Deletion of multiple exons
+^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+A deletion of 10.26 kb (``chr17:43,100,079-43,110,335del``) affecting *BRCA1* that was assigned a *PSV* score of 427.00.
+
+The deletion affects three *BRCA1* exons. Pathogenic variants in *BRCA1* are associated with
+Breast-ovarian cancer, familial, 1 (``OMIM:604370``).
+
+The phenotypic feature curated for this case was:
+
+* ``HP:0003002`` Breast carcinoma
+
+Data were curated from a published case report `The first case report of a large deletion of the BRCA1 gene in Croatia`_.
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0003002
+
+
+
+Deletion of multiple genes
+^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+Deletion of 481.73 kb (``chr2:109,923,337-110,405,062del``) affecting *MTLN*, *MALL*, *MTLN*, and *NPHP1*
+that was assigned a *PSV* score of 17.60.
+
+Pathogenic variants in *NPHP1* are associated with Joubert syndrome 4 (``OMIM:609583``).
+
+The phenotypic features curated for this case were:
+
+* ``HP:0003774`` Stage 5 chronic kidney disease
+* ``HP:0001320`` Cerebellar vermis hypoplasia
+* ``HP:0002078`` Truncal ataxia
+* ``HP:0000618`` Blindness
+* ``HP:0000508`` Ptosis
+* ``HP:0002419`` Molar tooth sign on MRI
+* ``HP:0011933`` Elongated superior cerebellar peduncle
+* ``HP:0002070`` Limb ataxia
+* ``HP:0000543`` Optic disc pallor
+* ``HP:0000589`` Coloboma
+
+Data were curated from a published case report `Whole-exome sequencing and digital PCR identified a novel compound heterozygous mutation in the NPHP1 gene in a case of Joubert syndrome and related disorders`_.
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0003774 --term HP:0001320 --term HP:0002078 --term HP:0000618 --term HP:0000508 --term HP:0002419 --term HP:0011933 --term HP:0002070 --term HP:0000543 --term HP:0000589
+
+
+
+Duplication of coding sequence
+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+Duplication of 36 bp (``chr13:72835296-72835332dup``) affecting *PIBF1* that was assigned a *PSV* score of 3.38.
+Pathogenic variants in *PIBF1* are associated with Joubert syndrome 33 (``OMIM:617767``).
+
+The phenotypic features curated for this case were:
+
+* ``HP:0032417`` Periglomerular fibrosis
+* ``HP:0000076`` Vesicoureteral reflux
+* ``HP:0002079`` Hypoplasia of the corpus callosum
+* ``HP:0001541`` Ascites
+* ``HP:0000540`` Hypermetropia
+* ``HP:0011968`` Feeding difficulties
+* ``HP:0001250`` Seizure
+* ``HP:0000490`` Deeply set eye
+* ``HP:0001263`` Global developmental delay
+* ``HP:0001284`` Areflexia
+* ``HP:0002240`` Hepatomegaly
+* ``HP:0001290`` Generalized hypotonia
+* ``HP:0031200`` Hyaline casts
+* ``HP:0011800`` Midface retrusion
+* ``HP:0000090`` Nephronophthisis
+* ``HP:0000092`` Renal tubular atrophy
+* ``HP:0001919`` Acute kidney injury
+* ``HP:0012650`` Perisylvian polymicrogyria
+* ``HP:0002419`` Molar tooth sign on MRI
+* ``HP:0002119`` Ventriculomegaly
+* ``HP:0000105`` Enlarged kidney
+
+Data were curated from a published case report `A biallelic 36-bp insertion in PIBF1 is associated with Joubert syndrome`_
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0032417 --term HP:0000076 --term HP:0002079 --term HP:0001541 --term HP:0000540 --term HP:0011968 --term HP:0001250 --term HP:0000490 --term HP:0001263 --term HP:0001284 --term HP:0002240 --term HP:0001290 --term HP:0031200 --term HP:0011800 --term HP:0000090 --term HP:0000092 --term HP:0001919 --term HP:0012650 --term HP:0002419 --term HP:0002119 --term HP:0000105
+
+
+
+Multigene inversion
+^^^^^^^^^^^^^^^^^^^
+
+Inversion of ~12.23 kb (``inv(chr3)(9725702; 9737931)``) that disrupts the coding sequence of *BRPF1* was assigned
+*PSV* score of 9.25.
+
+Pathogenic variants in *BRPF1* are associated with Intellectual developmental disorder with dysmorphic facies and ptosis ``OMIM:617333``.
+
+The phenotypic features curated for this case were:
+
+* ``HP:0000316`` Hypertelorism
+* ``HP:0000494`` Downslanted palpebral fissures
+* ``HP:0000431`` Wide nasal bridge
+* ``HP:0000286`` Epicanthus
+* ``HP:0000311`` Round face
+* ``HP:0012368`` Flat face
+* ``HP:0000486`` Strabismus
+* ``HP:0000508`` Ptosis
+* ``HP:0002949`` Fused cervical vertebrae
+* ``HP:0002194`` Delayed gross motor development
+* ``HP:0000750`` Delayed speech and language development
+* ``HP:0002342`` Intellectual disability, moderate
+* ``HP:0011150`` Myoclonic absence seizure
+* ``HP:0002069`` Bilateral tonic-clonic seizure
+* ``HP:0001252`` Hypotonia
+
+
+Data were curated from a published case report `Pathogenic 12-kb copy-neutral inversion in syndromic intellectual disability identified by high-fidelity long-read sequencing`_
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0000286 --term HP:0002069 --term HP:0000494 --term HP:0002342 --term HP:0000486 --term HP:0000750 --term HP:0000431 --term HP:0001252 --term HP:0002194 --term HP:0012368 --term HP:0011150 --term HP:0002949 --term HP:0000508 --term HP:0000316 --term HP:0000311
+
+
+
+Deletion affecting transcription start site
+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+Deletion of ∼1.57 kb (``chrX:64,205,190-64,206,761del``) affecting transcription start site of *AMER1* was assigned
+*PSV* score of 10.39.
+
+Pathogenic variants in *AMER1* are associated with Osteopathia striata with cranial sclerosis (``OMIM:300373``).
+
+The phenotypic features curated for this case were:
+
+* ``HP:0001561`` Polyhydramnios
+* ``HP:0002684`` Thickened calvaria
+* ``HP:0000256`` Macrocephaly
+* ``HP:0000316`` Hypertelorism
+* ``HP:0031367`` Metaphyseal striations
+* ``HP:0002744`` Bilateral cleft lip and palate
+* ``HP:0002781`` Upper airway obstruction
+* ``HP:0001004`` Lymphedema
+* ``HP:0000750`` Delayed speech and language development
+
+Data were curated from a published case report `Deletion of Exon 1 in AMER1 in Osteopathia Striata with Cranial Sclerosis`_.
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0001561 --term HP:0000750 --term HP:0002684 --term HP:0002781 --term HP:0000316 --term HP:0031367 --term HP:0002744 --term HP:0000256 --term HP:0001004
+
+
+
+Deletion affecting promoter region
+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+A deletion of 13 bp (``chr12:6,124,705-6,124,718del``) located in the core promoter region of *VWF* was assigned *PSV* score of
+64.18.
+
+In the original publication, the deletion was shown to lead to aberrant binding of Ets transcription factors to the site
+of the deletion (30 bp upstream of *ENST00000261405.10*) and thereby reduce VWF expression.
+
+Pathogenic variants in *VWF* are associated with von Willebrand disease (``OMIM:193400``).
+
+The phenotypic features curated for this case were:
+
+* ``HP:0011890`` Prolonged bleeding following procedure
+* ``HP:0000978`` Bruising susceptibility
+* ``HP:0012147`` Reduced quantity of Von Willebrand factor
+
+Data were curated from a published case report `Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease`_.
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0011890 --term HP:0000978 --term HP:0012147
+
+
+
+Translocation disrupting a gene sequence
+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+A translocation (``t(chr3:11,007,014; chr4:139,383,334)``) affecting *SLC6A1* was assigned *PSV* score of 4.74.
+
+Pathogenic variants in *SLC6A1* are associated with Myoclonic-atonic epilepsy (``OMIM:616421``).
+
+The phenotypic features curated for this case were:
+
+* ``HP:0000252`` Microcephaly
+* ``HP:0000446`` Narrow nasal bridge
+* ``HP:0000272`` Malar flattening
+* ``HP:0000219`` Thin upper lip vermilion
+* ``HP:0000179`` Thick lower lip vermilion
+* ``HP:0002650`` Scoliosis
+* ``HP:0002987`` Elbow flexion contracture
+* ``HP:0006380`` Knee flexion contracture
+* ``HP:0001250`` Seizure
+* ``HP:0001263`` Global developmental delay
+* ``HP:0001276`` Hypertonia
+
+
+Data were curated from a published case report `Phenotypic consequences of gene disruption by a balanced de novo translocation involving SLC6A1 and NAA15`_
+
+Command
+~~~~~~~
+
+.. code-block:: console
+
+    $ java -jar svanna-cli.jar prioritize -c svanna-config.yml --vcf example.vcf --term HP:0000252 --term HP:0000446 --term HP:0000272 --term HP:0000219 --term HP:0000179 --term HP:0002650 --term HP:0002987 --term HP:0006380 --term HP:0001250 --term HP:0001263 --term HP:0001263 --term HP:0001276
+
+
+
+.. _examples.vcf: https://github.com/TheJacksonLaboratory/Squirls/blob/development/squirls-cli/src/examples/example.vcf
+.. _Decoding NF1 Intragenic Copy-Number Variations: https://pubmed.ncbi.nlm.nih.gov/26189818
+.. _The first case report of a large deletion of the BRCA1 gene in Croatia: https://pubmed.ncbi.nlm.nih.gov/29310340
+.. _Whole-exome sequencing and digital PCR identified a novel compound heterozygous mutation in the NPHP1 gene in a case of Joubert syndrome and related disorders: https://pubmed.ncbi.nlm.nih.gov/28347285
+.. _A biallelic 36-bp insertion in PIBF1 is associated with Joubert syndrome: https://pubmed.ncbi.nlm.nih.gov/29695797
+.. _Pathogenic 12-kb copy-neutral inversion in syndromic intellectual disability identified by high-fidelity long-read sequencing: https://pubmed.ncbi.nlm.nih.gov/33157260
+.. _Deletion of Exon 1 in AMER1 in Osteopathia Striata with Cranial Sclerosis: https://pubmed.ncbi.nlm.nih.gov/33265914
+.. _Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease: https://pubmed.ncbi.nlm.nih.gov/20696945
+.. _Phenotypic consequences of gene disruption by a balanced de novo translocation involving SLC6A1 and NAA15: https://pubmed.ncbi.nlm.nih.gov/29621621

docs/index.rst

@@ -16,6 +16,7 @@ of germline variants.
    running
    outputformats
    tutorial
+   examples
 
 
 .. enhancers

docs/outputformats.rst

@@ -10,7 +10,7 @@ to select one or more of the desired output formats (e.g. ``--output-format html
 HTML output format
 ^^^^^^^^^^^^^^^^^^
 
-SvAnna creates an *HTML* file with the analysis summary and with variants sorted by the :math:`TAD_{SV}` score
+SvAnna creates an *HTML* file with the analysis summary and with variants sorted by the :math:`PSV` score
 in descending order.
 By default, top 100 variants are included into the report. The number of the reported variants can be adjusted by
 the ``--report-top-variants`` option.
@@ -26,14 +26,14 @@ The report consists of several parts:
 .. note::
   Only the variants that passed all the filters are visualized in the *Prioritized SVs* section
 
-The ``--no-breakends`` excludes breakend/translocation variants from the report.
+The ``--no-breakends`` option excludes breakends/translocations from the report.
 
 VCF output format
 ^^^^^^^^^^^^^^^^^
 When including ``vcf`` into the ``--output-format`` option, a VCF file with all input variants is created.
 The prioritization adds a novel *INFO* field to each variant:
 
-* ``TADSV`` - an *INFO* field containing :math:`TAD_{SV}` score for the variant.
+* ``PSV`` - an *INFO* field containing :math:`PSV` score for the variant.
 
 .. note::
   * ``--report-top-variants`` option has no effect for the *VCF* output format.
@@ -54,12 +54,12 @@ The results are written into a tabular file with the following columns:
 * *failed_filters* - the names of filters that the variant failed to pass. The names are separated by semicolon (``;``)
   * ``filter`` - the variant failed previous VCF filters - at least one filter flag is present in the variant VCF line, except for ``PASS``.
   * ``coverage`` - the variant is supported by less reads than specified by ``--min-read-support`` option
-* *tadsv* - the :math:`TAD_{SV}` score value
+* *psv* - the :math:`PSV` score value
 
 .. table:: Tabular output
 
   ======== ========= ========== ====== ======= ================= =====================
-   contig    start      end       id    vtype   failed_filters         tadsv
+   contig    start      end       id    vtype   failed_filters         psv
   ======== ========= ========== ====== ======= ================= =====================
    11       31130456  31671718   abcd   DEL                       109.75766900764305
    18       46962113  46969912   efgh   DUP     filter;coverage   3.2