Merge branch 'development'

Author: julesjacobsen

docs/advanced_analysis.rst

@@ -491,24 +491,44 @@ frequency higher than the stated percentage in any database defined in the :ref:
 pathogenicityFilter:
 ....................
 Will apply the pathogenicity scores defined in the :ref:`pathogenicitySources<pathogenicitysources>` section to variants.
-If the ``keepNonPathogenic`` field is set to ``true`` then all variants will be kept. Setting this to ``false`` will set
-the filter to fail non-missense variants with pathogenicity scores lower than a score cutoff of 0.5.
-
 This filter is meant to be quite permissive and we recommend it be set to ``true`` unless running genomiser
-(i.e. including REMM/CADD/SPLICE_AI and all non-coding regions), in which case setting ``keepNonPathogenic: false`` is
-recommended as Exomiser will use a stringent cutoff to remove variants with a `CADD <https://cadd.bihealth.org/info>`_
-raw score <= 15.0 a `REMM score <https://doi.org/10.1093/gigascience/giad024>`_ <= 0.914
-or a `SpliceAI <https://doi.org/10.1016/j.cell.2018.12.015>`_ <= 0.1 These thresholds were chosen based on the
-recommendations of the authors of the scores.
+(i.e. including REMM/CADD/SPLICE_AI and all non-coding regions).
+
+If ``keepNonPathogenic`` is set to ``true``, all variants will pass regardless of their pathogenicity scores.
+
+If ``keepNonPathogenic`` is set to ``false``, the ``target`` field controls which variants are subject to filtering:
+
+- ``target: ALL`` — both coding and non-coding variants are filtered. Coding variants are failed if they have a
+  pathogenicity score < 0.5, non-coding variants are filtered using the thresholds described below.
+- ``target: NON_CODING`` (recommended for WGS) — only non-coding variants are filtered using the thresholds below;
+  all coding variants pass. For WES samples this is equivalent to ``keepNonPathogenic: true``, since non-coding
+  variants are absent.
+
+Non-coding variants (when subject to filtering) must exceed at least one of the following thresholds to pass:
+
+- `CADD <https://cadd.bihealth.org/info>`_ scaled score (Exomiser raw score) >= 15.0
+- `SpliceAI <https://doi.org/10.1016/j.cell.2018.12.015>`_ score > 0.1
+- `REMM <https://doi.org/10.1093/gigascience/giad024>`_ score > 0.914
+
+These thresholds were chosen based on the recommendations of the respective score authors. Scores are optional; a
+variant only needs to exceed one present score to pass.
+
+We recommend ``keepNonPathogenic: true`` for standard exome analysis. For whole-genome analysis including non-coding
+regions (e.g. using REMM/CADD/SpliceAI), use ``keepNonPathogenic: false`` with ``target: NON_CODING``.
 
 .. code-block:: yaml
 
+    # Either (recommended for WES/Exomiser)
     pathogenicityFilter: {keepNonPathogenic: true}
+    # Or (recommended for WGS/Genomiser)
+    pathogenicityFilter: {keepNonPathogenic: false, target: NON_CODING}
+    # Or (most stringent may result in reduced recall due to loss of false negatives)
+    pathogenicityFilter: {keepNonPathogenic: false, target: ALL}
 
 
 .. important::
 
-    Not defining this filter will result in all variants having no pathogenicity data or ClinVar annotations, even if the
+    Not defining this filter will result in variants having no pathogenicity data or ClinVar annotations, even if the
     :ref:`pathogenicitySources<pathogenicitysources>` are defined. Failing to include this will result in Exomiser
     using default scores based on the assigned variant effect. If you want to score all variants and write failed ones
     to the output, it is recommended to use `analysisMode: FULL`.

docs/conf.py

@@ -59,9 +59,9 @@
 author = u'Jules Jacobsen, Damian Smedley, Peter Robinson'
 
 # The short X.Y version
-version = u'15.0.0'
-genome_data_version = u'2512'
-phenotype_data_version = u'2512'
+version = u'15.1.0'
+genome_data_version = u'2602'
+phenotype_data_version = u'2602'
 # The full version, including alpha/beta/rc tags
 release = version
 

exomiser-cli/CHANGELOG.md

@@ -1,5 +1,17 @@
 # The Exomiser Command Line Interface - Changelog
 
+## 15.1.0 2026-06-09
+- The `pathogenicityFilter` now has a `target` option to specify whether to filter non-coding variants. The default is
+  `ALL` but `NON_CODING` can be specified to filter non-coding variants. This change only affects variants found in 
+  non-coding regions. We recommend using the standard `pathogenicityFilter{keepNonPathogenic: true}` for exome analysis, 
+  but when running genomiser (i.e. including REMM/CADD/SPLICE_AI and all non-coding regions) or any analysis including
+  non-coding regions, use `pathogenicityFilter{keepNonPathogenic: false, target: NON_CODING}`. See the [documentation](https://exomiser.readthedocs.io/en/stable/advanced_analysis.html#pathogenicityfilter)
+  for more details.
+
+- Fix for issue [#629](https://github.com/exomiser/Exomiser/issues/629) - replace commas in disease names with semicolons.
+- Fix for issue [#633](https://github.com/exomiser/Exomiser/issues/633) - calculate variant score for non-symbolic insertions > 1kb.
+- Change for issue [#635](https://github.com/exomiser/Exomiser/issues/635) - Display CADD phred scores alongside the scaled scores in HTML.
+
 ## 15.0.0 2026-02-28
 [![Rare Disease Day](https://www.rarediseaseday.org/wp-content/uploads/Rare-disease-day-logo.svg
 )](https://www.rarediseaseday.org)

exomiser-cli/README.md

@@ -223,8 +223,8 @@ It is important to note that if an authentication issue arises, it may be necess
 file to include authentication for `https://index.docker.io/v1/`. 
 This can be done by providing your base64-encoded Docker credentials.
 
-Docker images are build using [jib](https://github.com/GoogleContainerTools/jib/tree/master/jib-maven-plugin#quickstart)
-which does not require a Docker daemon to be running/installed in order to build an image. 
+Docker images are built using [jib](https://github.com/GoogleContainerTools/jib/tree/master/jib-maven-plugin#quickstart)
+which does not require a Docker daemon to be running/installed to build an image. 
 
 
 ```shell
@@ -235,92 +235,99 @@ ${docker.repository}/exomiser-cli           latest           f39698e3f36b  53 ye
 ${docker.repository}/exomiser-cli           ${project.version} f39698e3f36b  53 years ago   274 MB
 ```
 
-### <a id="working-with-the-distroless-image"></a>Working with the distroless image (no shell)
+### <a id="docker-environment-variables"></a>Docker environment variables
 
-Distroless images are the default image and come without a shell. These are can be pulled using 
-`docker pull ${docker.registry}/${docker.repository}/exomiser-cli:latest` or better `docker pull ${docker.registry}/${docker.repository}/exomiser-cli:${project.version}`
+Exomiser requires data directory and version configuration. The Docker images include a preconfigured environment variable `EXOMISER_DATA_DIRECTORY=/exomiser-data`.
 
-If you choose to run the distroless image use the following command:
+**Option 1: Set environment variables directly**
 
 ```shell
- docker run -v "/path/to/exomiser-data:/exomiser-data" \
- -v "/path/to/exomiser/exomiser-config/:/exomiser"  \
- -v "/path/to/exomiser/results:/results"  \
- ${docker.repository}/exomiser-cli:${project.version}  \
- analyse --analysis /exomiser/test-analysis-exome.yml  \
- --spring.config.location=/exomiser/application.properties
+-e EXOMISER_HG19_DATA_VERSION=2512 \
+-e EXOMISER_PHENOTYPE_DATA_VERSION=2512
 ```
 
-or using Spring configuration arguments instead of the `application.properties`:
+**Option 2: Use an application.properties file**
+Mount your file and point Spring to it: `application.properties`
 
 ```shell
- docker run -v "/path/to/exomiser-data:/exomiser-data" \
- -v "/path/to/exomiser/exomiser-config/:/exomiser"  \
- -v "/path/to/exomiser/results:/results"  \
- ${docker.repository}/exomiser-cli:${project.version}  \
- analyse --analysis /exomiser/test-analysis-exome.yml  \
- # minimal requirements for an hg19 exome sample
- --exomiser.data-directory=/exomiser-data \
- --exomiser.hg19.data-version=${genome.data.version} \
- --exomiser.phenotype.data-version=${phenotype.data.version}
+-v /path/to/application.properties:/config/application.properties \
+-e SPRING_CONFIG_LOCATION=/config/application.properties
 ```
------
 
-In both cases, to run the image you will need the standard Exomiser directory layout to mount as separate volumes as in the CLI and
-supply an `application.properties` file or environmental variables to point to the data required _e.g._
+### Docker image types
+Exomiser provides two image types:
+- Distroless (default): Minimal security-hardened image without a shell. Tagged as `:latest` or `:${project.version}`
+- Bash: Includes a shell for interactive use, required for NextFlow. Tagged as `:latest-bash` or `:${project.version}-bash`
 
-Keep in mind to update your `application.properties` to point the data to the location
-inside the container, like:
+### Required volumes and directory structure
+Both image types require mounting three directories:
 
+```shell
+-v "/host/path/to/exomiser-data:/exomiser-data"  # Contains unpacked data directories like 2512_hg19
+-v "/host/path/to/exomiser-cli/examples/:/examples"            # Analysis files and test data
+-v "/host/path/to/results:/results"              # Output directory for results
+```
 
-```application.properties
-exomiser.data-directory=/exomiser-data
+Example data directory structure:
+
+```
+exomiser-data/
+├── 2512_hg19/
+└── 2512_phenotype/
 ```
 
------
-### <a id="working-with-the-docker-bash-image"></a>Working with the docker bash images
+### Working with the distroless image
+
+Pull the image:
 
-Running the image with the following command will open the shell and create volumes with
-links to the exomiser data and connects the results to your local machine. `/results` should be an empty directory,
-where Exomiser will write the results into.
+``` shell
+docker pull ${docker.registry}/${docker.repository}/exomiser-cli:${project.version}
+```
 
+Run Exomiser (the exomiser command is the entrypoint, so pass arguments directly):
 
 ```shell
-docker run -v "/path/to/exomiser-data:/exomiser-data" \
- -v "/path/to/exomiser/exomiser-config/:/exomiser" \
- -v "/path/to/exomiser/results:/results"  \
- ${docker.repository}/exomiser-cli:${project.version}-bash  
+docker run \
+-v "/host/path/to/exomiser-data:/exomiser-data" \
+-v "/host/path/to/exomiser-cli/examples/:/examples" \
+-v "/host/path/to/results:/results" \
+-e EXOMISER_HG19_DATA_VERSION=2512 \
+-e EXOMISER_PHENOTYPE_DATA_VERSION=2512 \
+${docker.repository}/exomiser-cli:${project.version} \
+analyse --analysis /examples/preset-exome-analysis-human-only.yml \
+--vcf /examples/Pfeiffer.vcf.gz --assembly hg19 \
+--sample /examples/pfeiffer-phenopacket.yml \
+--output-directory /results --output-format=PARQUET --output-filename docker-test
 ```
 
-Here the contents of `/path/to/exomiser/exomiser-config` is simply the `application.properties` file and the example files
-to test all is working correctly.
+Working with the bash image
+Pull the image:
 
 ```shell
-$ tree /path/to/exomiser/exomiser-config/
-exomiser-config/
-├── application.properties
-├── Pfeiffer.vcf.gz
-├── Pfeiffer.vcf.gz.tbi
-└── test-analysis-exome.yml
+docker pull ${docker.registry}/${docker.repository}/exomiser-cli:${project.version}-bash
 ```
 
-#### Running Exomiser from the bash shell
-After running the following commands Exomiser will be started from the containers shell.
+Start an interactive shell:
 
 ```shell
- source enable_exomiser.sh
- bash enable_exomiser.sh
- exomiser analyse --analysis /exomiser/test-analysis-exome.yml \
- --spring.config.location=/exomiser/application.properties
+docker run -it \
+ -v "/host/path/to/exomiser-data:/exomiser-data" \
+ -v "/host/path/to/exomiser-cli/examples/:/examples" \
+ -v "/host/path/to/results:/results" \
+ -e EXOMISER_HG19_DATA_VERSION=2512 \
+ -e EXOMISER_PHENOTYPE_DATA_VERSION=2512 \
+ ${docker.repository}/exomiser-cli:${project.version}-bash
 ```
 
-or using Spring configuration arguments instead of the `application.properties`:
+From the bash prompt, run Exomiser:
 
 ```shell
- exomiser --analysis /exomiser/test-analysis-exome.yml  \
- # minimal requirements for an hg19 exome sample
- --exomiser.data-directory=/exomiser-data \
- --exomiser.hg19.data-version=${genome.data.version} \
- --exomiser.phenotype.data-version=${phenotype.data.version}
+exomiser analyse --analysis /examples/preset-exome-analysis-human-only.yml \
+--vcf /examples/Pfeiffer.vcf.gz --assembly hg19 \
+--sample /examples/pfeiffer-phenopacket.yml \
+--output-directory /results --output-format=PARQUET --output-filename docker-test
 ```
+
+If successful, results will be written to /results/docker-test.parquet.
+
 -----

exomiser-cli/pom.xml

@@ -32,7 +32,7 @@
     <parent>
         <groupId>org.monarchinitiative.exomiser</groupId>
         <artifactId>exomiser</artifactId>
-        <version>15.0.0</version>
+        <version>15.1.0</version>
     </parent>
 
 
@@ -210,7 +210,7 @@
         <profile>
             <id>docker:bash</id>
             <properties>
-                <docker.base.image>eclipse-temurin:25.0.2_10-jre</docker.base.image>
+                <docker.base.image>eclipse-temurin:25.0.2_10-jre@sha256:ff82c74a630c08b417502c4c18189e62074edbb28eb1f2d31b799ac138c01058</docker.base.image>
             </properties>
             <build>
                 <plugins>
@@ -225,6 +225,7 @@
                                     <goal>build</goal>
                                 </goals>
                                 <configuration>
+                                    <containerizingMode>packaged</containerizingMode>
                                     <from>
                                         <image>
                                             ${docker.base.image}
@@ -234,11 +235,6 @@
                                                 <os>linux</os>
                                                 <architecture>arm64</architecture>
                                             </platform>
-                                            <!-- No longer provided was this for MacOS? -->
-<!--                                            <platform>-->
-<!--                                                <os>linux</os>-->
-<!--                                                <architecture>arm</architecture>-->
-<!--                                            </platform>-->
                                             <platform>
                                                 <os>linux</os>
                                                 <architecture>amd64</architecture>
@@ -258,16 +254,25 @@
                                         <entrypoint>
                                             <arg>/bin/bash</arg>
                                         </entrypoint>
+                                        <environment>
+                                            <EXOMISER_DATA_DIRECTORY>/exomiser-data</EXOMISER_DATA_DIRECTORY>
+                                        </environment>
                                         <volumes>
                                             <volume>/exomiser-data</volume>
-                                            <volume>/exomiser</volume>
                                             <volume>/results</volume>
                                         </volumes>
                                     </container>
                                     <extraDirectories>
+                                        <paths>
+                                            <path>
+                                                <from>src/main/jib</from>
+                                                <into>/usr/local/bin</into>
+                                                <includes>exomiser</includes>
+                                            </path>
+                                        </paths>
                                         <permissions>
                                             <permission>
-                                                <file>/entrypoint.sh</file>
+                                                <file>/usr/local/bin/exomiser</file>
                                                 <mode>755</mode>
                                             </permission>
                                         </permissions>
@@ -294,6 +299,7 @@
                                     <goal>build</goal>
                                 </goals>
                                 <configuration>
+                                    <containerizingMode>packaged</containerizingMode>
                                     <from>
                                         <image>
                                             ${docker.base.image}
@@ -320,9 +326,11 @@
                                         </tags>
                                     </to>
                                     <container>
+                                        <environment>
+                                            <EXOMISER_DATA_DIRECTORY>/exomiser-data</EXOMISER_DATA_DIRECTORY>
+                                        </environment>
                                         <volumes>
                                             <volume>/exomiser-data</volume>
-                                            <volume>/exomiser</volume>
                                             <volume>/results</volume>
                                         </volumes>
                                     </container>