From 09532cf8574e27ee0d2cf5b3d5e8555fd611f59a Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 10:22:59 +0100 Subject: [PATCH 01/10] Write introduction to the annotation pipeline --- annotation_pipeline/README.md | 7 +++++++ 1 file changed, 7 insertions(+) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index dda58391..68f41949 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -1,3 +1,10 @@ +# IMPC Annotation Pipeline +The IMPC annotation pipeline assigns Mammalian Phenotype (MP) terms to significant genetic effects based on a p-value threshold of 0.0001. The goal is to associate phenotypic observations with the corresponding genetic modifications. +At the IMPC, genetic effects are identified using three statistical analysis platforms: +1. Linear Mixed Model framework or MM +2. Fisher Exact Test framework or FE +3. Reference Range Plus Test framework or RR + ```mermaid %%{ init: { From 34232f8aa4579221f6f5a66b293e0fdb2fbd29a5 Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 10:35:06 +0100 Subject: [PATCH 02/10] Write about MP chooser --- annotation_pipeline/README.md | 3 +++ 1 file changed, 3 insertions(+) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 68f41949..4223a906 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -5,6 +5,9 @@ At the IMPC, genetic effects are identified using three statistical analysis pla 2. Fisher Exact Test framework or FE 3. Reference Range Plus Test framework or RR +The annotation pipeline requires a reference table that summarises the available MP terms for a given IMPC parameter. This reference can be retrieved from [IMPReSS](https://www.mousephenotype.org/impress/index). +The ETL pipeline handles this by generating the `mp_chooser.json` file. + ```mermaid %%{ init: { From 653567f72a7d47ab8dbe8d8272978c2cda29902e Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 10:56:55 +0100 Subject: [PATCH 03/10] Write about IMPC data types --- annotation_pipeline/README.md | 10 +++++++++- 1 file changed, 9 insertions(+), 1 deletion(-) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 4223a906..85384680 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -2,9 +2,17 @@ The IMPC annotation pipeline assigns Mammalian Phenotype (MP) terms to significant genetic effects based on a p-value threshold of 0.0001. The goal is to associate phenotypic observations with the corresponding genetic modifications. At the IMPC, genetic effects are identified using three statistical analysis platforms: 1. Linear Mixed Model framework or MM -2. Fisher Exact Test framework or FE +2. Fisher's Exact Test framework or FE 3. Reference Range Plus Test framework or RR +## Continuous data +Continuous data are typically analysed using a linear mixed model framework. These continuous measurements are particularly informative because the direction of change can be determined through the effect size. + +However, due to the complexity of the data, not all continuous variables can be analysed using this framework. In such cases, the IMPC often employs the Reference Range Plus (RR) method. Control data are first discretising into three categories: low, normal, and high. Mutant data points are then classified into one of these reference categories. Finally, a Fisher's Exact Test is applied to determine whether there is a statistically significant deviation from the normal category. + +## Categorical data +Categorical data in the IMPC encompasses a range of qualitative measurements and is analysed using Fisher’s Exact Test, as implemented in the R package OpenStats. + The annotation pipeline requires a reference table that summarises the available MP terms for a given IMPC parameter. This reference can be retrieved from [IMPReSS](https://www.mousephenotype.org/impress/index). The ETL pipeline handles this by generating the `mp_chooser.json` file. From 750e6e817cd2cacfe15d989eec4a931a517245c2 Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 12:26:21 +0100 Subject: [PATCH 04/10] Write about annotationChooser function --- annotation_pipeline/README.md | 3 +++ 1 file changed, 3 insertions(+) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 85384680..89107bb0 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -13,6 +13,9 @@ However, due to the complexity of the data, not all continuous variables can be ## Categorical data Categorical data in the IMPC encompasses a range of qualitative measurements and is analysed using Fisher’s Exact Test, as implemented in the R package OpenStats. +# How IMPC Annotation Pipeline Works +The `annotationChooser` function is processes statistical analysis results called statpacket. It determines calls based on significance levels. These calles are then mapped to Mammalian Phenotype (MP) ontology terms using a provided `mp_chooser_file`. Finally, it updates the input statpacket's JSON component with the identified MP terms. If no relevant annotation is found or the statistical result is not significant, it returns the original statpacket with no MP terms added. + The annotation pipeline requires a reference table that summarises the available MP terms for a given IMPC parameter. This reference can be retrieved from [IMPReSS](https://www.mousephenotype.org/impress/index). The ETL pipeline handles this by generating the `mp_chooser.json` file. From 8fcc38512311b964795f4f3e10cf8676dfd98955 Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 13:06:19 +0100 Subject: [PATCH 05/10] Update flowchart --- annotation_pipeline/README.md | 33 +++++++++++++++++++++++++-------- 1 file changed, 25 insertions(+), 8 deletions(-) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 89107bb0..330d820e 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -19,6 +19,22 @@ The `annotationChooser` function is processes statistical analysis results calle The annotation pipeline requires a reference table that summarises the available MP terms for a given IMPC parameter. This reference can be retrieved from [IMPReSS](https://www.mousephenotype.org/impress/index). The ETL pipeline handles this by generating the `mp_chooser.json` file. +- We will denote p-value calls made from: + - ♂ Male only data + - ♀ Female only data + - ⚤ All data combined + +- We will denote `mp_chooser.json` terms as they are: + - MALE + - FEMALE + - UNSPECIFIED + +In the `mp_chooser.json` file each MP term can have different levels: +- Ontology term levels: ABNORMAL, INCREASE, DECREASE. +- Sex levels: FEMALE, MALE and UNSPECIFIED. + +MP term assignment logic can be seen below: + ```mermaid %%{ init: { @@ -32,11 +48,12 @@ The ETL pipeline handles this by generating the `mp_chooser.json` file. } }%% graph TD; - A[Repeat separately for Overall, Females and Males] --> B{Is genotype effect significant?} - B -- No --> C[Do not assign MP term] - B -- Yes --> D{Is the direction of genotype effect specified?} - D -- No --> E[Select Abnormal term] - D -- Yes --> F{Is there any conflict of direction?
example: Low.Decrease/High.Increase
or Male.Decrease/Female.Increase} - F -- No --> G[Choose an MP term corresponding to the direction of change] - F -- Yes --> H[Select Abnormal term] -``` \ No newline at end of file + Start{Which method is used for the analysis?} --> |MM| MM[Prioritise INCREASE/DECREASE MP term] --> A + Start --> |FE or RR| FE_RR[Only use ABNORMAL MP term] --> A + + A{"Is FEMALE/MALE specific MP term available in the mp_chooser file?"} + A --> |Yes| A2[Use sex specific MP term] --> B{Is ♀/♂ call observed?} + A --> |No| A3[Use UNSPECIFIED term] --> B + + B --> |Yes| B1[Drop UNSPECIFIED and report sex-specific MP term] + B --> |No| B2[Keep and report UNSPECIFIED MP term] From 34547b24e403f9e59c20e642e03fa1d48ff61015 Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 13:43:31 +0100 Subject: [PATCH 06/10] Fix typos --- annotation_pipeline/README.md | 8 ++++---- 1 file changed, 4 insertions(+), 4 deletions(-) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 330d820e..825c6d7c 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -8,13 +8,13 @@ At the IMPC, genetic effects are identified using three statistical analysis pla ## Continuous data Continuous data are typically analysed using a linear mixed model framework. These continuous measurements are particularly informative because the direction of change can be determined through the effect size. -However, due to the complexity of the data, not all continuous variables can be analysed using this framework. In such cases, the IMPC often employs the Reference Range Plus (RR) method. Control data are first discretising into three categories: low, normal, and high. Mutant data points are then classified into one of these reference categories. Finally, a Fisher's Exact Test is applied to determine whether there is a statistically significant deviation from the normal category. +However, due to the complexity of the data, not all continuous variables can be analysed using this framework. In such cases, the IMPC often employs the Reference Range Plus (RR) method. Control data are first discretised into three categories: low, normal, and high. Mutant data points are then classified into one of these reference categories. Finally, a Fisher's Exact Test is applied to determine whether there is a statistically significant deviation from the normal category. ## Categorical data Categorical data in the IMPC encompasses a range of qualitative measurements and is analysed using Fisher’s Exact Test, as implemented in the R package OpenStats. # How IMPC Annotation Pipeline Works -The `annotationChooser` function is processes statistical analysis results called statpacket. It determines calls based on significance levels. These calles are then mapped to Mammalian Phenotype (MP) ontology terms using a provided `mp_chooser_file`. Finally, it updates the input statpacket's JSON component with the identified MP terms. If no relevant annotation is found or the statistical result is not significant, it returns the original statpacket with no MP terms added. +The `annotationChooser` function processes statistical analysis results called statpackets. It determines calls based on significance levels. These calls are then mapped to Mammalian Phenotype (MP) ontology terms using a provided `mp_chooser_file`. Finally, it updates the input statpacket's JSON component with the identified MP terms. If no relevant annotation is found or the statistical result is not significant, it returns the original statpacket with no MP terms added. The annotation pipeline requires a reference table that summarises the available MP terms for a given IMPC parameter. This reference can be retrieved from [IMPReSS](https://www.mousephenotype.org/impress/index). The ETL pipeline handles this by generating the `mp_chooser.json` file. @@ -30,7 +30,7 @@ The ETL pipeline handles this by generating the `mp_chooser.json` file. - UNSPECIFIED In the `mp_chooser.json` file each MP term can have different levels: -- Ontology term levels: ABNORMAL, INCREASE, DECREASE. +- Ontology term levels: ABNORMAL, INCREASED, DECREASED. - Sex levels: FEMALE, MALE and UNSPECIFIED. MP term assignment logic can be seen below: @@ -48,7 +48,7 @@ MP term assignment logic can be seen below: } }%% graph TD; - Start{Which method is used for the analysis?} --> |MM| MM[Prioritise INCREASE/DECREASE MP term] --> A + Start{Which method is used for the analysis?} --> |MM| MM[Prioritise INCREASED/DECREASED MP term, otherwise use ABNORMAL] --> A Start --> |FE or RR| FE_RR[Only use ABNORMAL MP term] --> A A{"Is FEMALE/MALE specific MP term available in the mp_chooser file?"} From 06ede99d1cf21b8490ff95fcd2cff647149401df Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Fri, 13 Jun 2025 13:45:05 +0100 Subject: [PATCH 07/10] Remove IMPC_annotation_documentation.pdf --- .../IMPC_annotation_documentation.pdf | Bin 256661 -> 0 bytes 1 file changed, 0 insertions(+), 0 deletions(-) delete mode 100644 annotation_pipeline/IMPC_annotation_documentation.pdf diff --git a/annotation_pipeline/IMPC_annotation_documentation.pdf b/annotation_pipeline/IMPC_annotation_documentation.pdf deleted file 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z=7a){b<4iMmI(^EJyuZYAA;1s*9TCj-kzU1VcY<1<{iB|a|9Gqv9yD>ww0J#Xv55x4z?6Ap)R-_Zj$2)AVjFt9PXRUZNjc+njh^bb?*pX;B# zfj}UD Date: Tue, 24 Jun 2025 11:47:44 +0100 Subject: [PATCH 08/10] Clarify information in the annotation pipeline documentation --- annotation_pipeline/README.md | 12 +++++++----- 1 file changed, 7 insertions(+), 5 deletions(-) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 825c6d7c..dc0680e4 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -31,7 +31,9 @@ The ETL pipeline handles this by generating the `mp_chooser.json` file. In the `mp_chooser.json` file each MP term can have different levels: - Ontology term levels: ABNORMAL, INCREASED, DECREASED. -- Sex levels: FEMALE, MALE and UNSPECIFIED. +- Sex levels: FEMALE, MALE, UNSPECIFIED. + +*Note:* Sex-specific MP terms, e.g. those with FEMALE and MALE sex levels, and UNSPECIFIED, are never encountered together for the same parameter. In other words, it is either a FEMALE/MALE term or an UNSPECIFIED term available in the `mp_chooser.json` file. MP term assignment logic can be seen below: @@ -51,9 +53,9 @@ graph TD; Start{Which method is used for the analysis?} --> |MM| MM[Prioritise INCREASED/DECREASED MP term, otherwise use ABNORMAL] --> A Start --> |FE or RR| FE_RR[Only use ABNORMAL MP term] --> A - A{"Is FEMALE/MALE specific MP term available in the mp_chooser file?"} - A --> |Yes| A2[Use sex specific MP term] --> B{Is ♀/♂ call observed?} + A{"Is sex-specific MP term available in the mp_chooser file?"} + A --> |Yes| A2[Use FEMALE/MALE term] --> B{Is ♀ or ♂ call observed?} A --> |No| A3[Use UNSPECIFIED term] --> B - B --> |Yes| B1[Drop UNSPECIFIED and report sex-specific MP term] - B --> |No| B2[Keep and report UNSPECIFIED MP term] + B --> |Yes| B1[Drop ⚤ call and report MP term for ♀ or ♂ call] + B --> |No| B2[Report ⚤ call] From 8276d40a9d2f2030198585c9ec91e7c3a0170e85 Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Wed, 25 Jun 2025 09:49:57 +0100 Subject: [PATCH 09/10] Write about statpacket --- annotation_pipeline/README.md | 4 +++- 1 file changed, 3 insertions(+), 1 deletion(-) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index dc0680e4..8dc6e11a 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -14,7 +14,9 @@ However, due to the complexity of the data, not all continuous variables can be Categorical data in the IMPC encompasses a range of qualitative measurements and is analysed using Fisher’s Exact Test, as implemented in the R package OpenStats. # How IMPC Annotation Pipeline Works -The `annotationChooser` function processes statistical analysis results called statpackets. It determines calls based on significance levels. These calls are then mapped to Mammalian Phenotype (MP) ontology terms using a provided `mp_chooser_file`. Finally, it updates the input statpacket's JSON component with the identified MP terms. If no relevant annotation is found or the statistical result is not significant, it returns the original statpacket with no MP terms added. +The `annotationChooser` function processes statistical analysis results called statpacket. It determines calls based on significance levels. These calls are then mapped to Mammalian Phenotype (MP) ontology terms using a provided `mp_chooser_file`. Finally, it updates the input statpacket's JSON component with the identified MP terms. If no relevant annotation is found or the statistical result is not significant, it returns the original statpacket with no MP terms added. + +*Note:* Several MP terms can be assign to one statpacket, because statpacket can have several "Active sex levels". The annotation pipeline requires a reference table that summarises the available MP terms for a given IMPC parameter. This reference can be retrieved from [IMPReSS](https://www.mousephenotype.org/impress/index). The ETL pipeline handles this by generating the `mp_chooser.json` file. From 96813ae447243f8b5a525cf21091f3c47835b237 Mon Sep 17 00:00:00 2001 From: Marina Kan Date: Thu, 26 Jun 2025 11:46:11 +0100 Subject: [PATCH 10/10] Add closing tick --- annotation_pipeline/README.md | 1 + 1 file changed, 1 insertion(+) diff --git a/annotation_pipeline/README.md b/annotation_pipeline/README.md index 8dc6e11a..b579efad 100644 --- a/annotation_pipeline/README.md +++ b/annotation_pipeline/README.md @@ -61,3 +61,4 @@ graph TD; B --> |Yes| B1[Drop ⚤ call and report MP term for ♀ or ♂ call] B --> |No| B2[Report ⚤ call] +```