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.legend { | ||
margin-top: 1em; | ||
padding: 0.5em; | ||
background-color: #f9f9f9; | ||
border-left: 4px solid #007acc; | ||
font-style: italic; | ||
} | ||
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/* Target the table with the specific class (if using one) */ | ||
.alt-rows-table { | ||
width: 100%; | ||
border-collapse: collapse; | ||
} | ||
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/* Style for table rows */ | ||
.alt-rows-table tr:nth-child(odd) { | ||
background-color: #f2f2f2; /* Light gray for odd rows */ | ||
} | ||
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.alt-rows-table tr:nth-child(even) { | ||
background-color: #ffffff; /* White for even rows */ | ||
} | ||
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/* Style for the header row */ | ||
.alt-rows-table th { | ||
background-color: #4CAF50; /* Change to your desired color (e.g., green) */ | ||
color: white; /* White text for contrast */ | ||
text-align: left; | ||
padding: 8px 12px; | ||
} | ||
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/* Optional: Add borders and padding to make the table more readable */ | ||
.alt-rows-table th, .alt-rows-table td { | ||
padding: 8px 12px; | ||
border: 1px solid #ddd; | ||
} | ||
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/* Optional: Add borders and padding to make the table more readable */ | ||
.alt-rows-table th, .alt-rows-table td { | ||
padding: 8px 12px; | ||
border: 1px solid #ddd; | ||
} | ||
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.alt-rows-table th { | ||
background-color: #4D4DFF; /* Light gray background for header */ | ||
text-align: left; | ||
} | ||
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figure .left-align { | ||
text-align: left; | ||
margin-top: 8px; /* Optional: Adjust spacing above the caption */ | ||
} | ||
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/* Highlight box for important sentences */ | ||
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border: 2px solid #4CAF50; /* Green border */ | ||
background-color: #f9f9f9; /* Light gray background */ | ||
padding: 12px; | ||
border-radius: 5px; /* Rounded corners */ | ||
font-size: 1rem; | ||
color: #333; /* Dark text */ | ||
margin: 10px 0; /* Spacing around the box */ | ||
} |
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# Disease annotations | ||
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The HPO team is transitioning to [GA4GH Phenopacket](https://phenopacket-schema.readthedocs.io/en/latest/){:target="\_blank"} format for annotating cases and diseases. We have created the | ||
[phenopacket store](https://github.com/monarch-initiative/phenopacket-store){:target="\_blank"} as a repository for individual-level information. We are working on the [pyphetools](https://monarch-initiative.github.io/pyphetools/){:target="\_blank"} package to streamline annotation of phenopackets. | ||
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Our software for this application is in development. We will discuss current options during the workshop. | ||
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## RareLink | ||
[RareLink](https://rarelink.readthedocs.io/en/latest/index.html){:target="\_blank"} is a new tool that enables efficient and accurate entry of HPO and other data related to rare disease medicine. | ||
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[RareLink](https://rarelink.readthedocs.io/en/latest/index.html){:target="\_blank"} is a tool for managing and processing rare disease data within the REDCap. RareLink aims to maximise the utility of REDCap by providing a comprehensive framework designed specifically for rare disease (RD) research and care. RareLink streamlines import of tabular data (e.g., Excel, relational database). | ||
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RareLink additionally provides a preconfigured data collection sheets based on the RD-CDM and user guides for manual data capture to ensure precision and correctness of data captured. Further, RareLink defines guidelines for developing more specialised REDCap sheets around the RD-CDM so that the data captured can also be processed by our framework to generate FHIR resources and Phenopackets. | ||
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RareLink is designed to be deployed and installed in a local REDCap instance. Using the guidelines provided, or using our preconfigured RareLink-REDCap and setting up the RareLink API, you can ensure that the data captured is compliant with the our framework to generate FHIR resources and Phenopackets. | ||
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We will typically provide a short introduction to RareLink at HPO workshops. |
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# Rules For Good HPO Structure | ||
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Creating a good HPO (see [here](good_term.md)) is not all we need to do. We also need to decide | ||
where to place the term in the HPO hierarchy. There are several rules of thumb that can help with this. | ||
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## True-Path Rule | ||
The true path rule (also known as annotation propagation rule) states: | ||
<div class="highlight-box"> | ||
If a term can be used to describe a patient then all parents of that term can be used to describe that patient. | ||
</div> | ||
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<figure markdown> | ||
![Phenopacket Schema](../img/cataract.png){ width="600" } | ||
<figcaption class="left-align"><b>Iridescent posterior subcapsular cataract</b>. | ||
Hierarchy for Iridescent posterior subcapsular cataract (HP:0007889). | ||
</figcaption> | ||
</figure> | ||
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In this case, if a patient is diagnosed with | ||
[Iridescent posterior subcapsular cataract (HP:0007889)](https://hpo.jax.org/browse/term/HP:0007889){:target="\_blank"}, it is true that the patient can also be said to have [Posterior subcapsular cataract (HP:0007787)](https://hpo.jax.org/browse/term/HP:0007889){:target="\_blank"}, because every *Iridescent posterior subcapsular cataract* is also a *Posterior subcapsular cataract* (i.e., *Iridescent posterior subcapsular cataract* is a specific kind of *Posterior subcapsular cataract*). | ||
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Similarly, the patient can be said to have a [Subcapsular cataract (HP:0000523)](https://hpo.jax.org/browse/term/HP:0000523) because every *Posterior subcapsular cataract* is also a *Subcapsular cataract*. The same thing is true of all of the ancesters, e.g., the patient can be said to have a | ||
[Cataract (HP:0000518)](https://hpo.jax.org/browse/term/HP:0000518){:target="\_blank"} and | ||
[Abnormal lens morphology (HP:0000517)](https://hpo.jax.org/browse/term/HP:0000517){:target="\_blank"} and so on up to the root of the ontology, [Phenotypic abnormality (HP:0000118)](https://hpo.jax.org/browse/term/HP:0000118){:target="\_blank"}. | ||
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## When is the true-path rule violated? | ||
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Consider the following example. Currently, in the HPO, [Cataract (HP:0000518)](https://hpo.jax.org/browse/term/HP:0000518){:target="\_blank"} is a subclass of | ||
[Abnormal lens morphology (HP:0000517)](https://hpo.jax.org/browse/term/HP:0000517){:target="\_blank"}. This is always true for reasons explained above. Let's say we decided to make | ||
[Cataract (HP:0000518)](https://hpo.jax.org/browse/term/HP:0000518){:target="\_blank"} also be a subclass of [Reduced visual acuity (HP:0007663)](https://hpo.jax.org/browse/term/HP:0007663){:target="\_blank"} | ||
because individuals with cataract tend to have vision problems. | ||
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This would violate the true-path rule, because it is not true that all individuals with cataract have reduced visual acuity. Rarely, visual acuity can be normal with certain kinds of congenital cataract. However, HPO-based software uses the true-path rule to infer that if a patient is explicitly annotated to a certain term, the patient is implicitly annotated to all of the ancestors of the term, which would not always be true in this example. | ||
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## Avoid bundled terms | ||
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Avoid creating terms that refer to multiple phenotypes that do not easily fit under a broader term. | ||
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For example, a concept such as "Bipolar disease I" is not a good HPO term because it is a diagnostic term that refers to an individual with a history of at least one manic episode who displays the following characteristics: | ||
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<table class="alt-rows-table"> | ||
<thead> | ||
<tr> | ||
<th>Label</th> | ||
<th>Description</th> | ||
</tr> | ||
</thead> | ||
<tbody> | ||
<tr> | ||
<td><b>A</b></td> | ||
<td>Distinct period of mood disturbance</td> | ||
</tr> | ||
<tr> | ||
<td><b>B</b></td> | ||
<td>Manic symptoms</td> | ||
</tr> | ||
<tr> | ||
<td><b>C</b></td> | ||
<td>Severe mood disturbance</td> | ||
</tr> | ||
<tr> | ||
<td><b>D</b></td> | ||
<td>Not attributable to a substance or other medical condition</td> | ||
</tr> | ||
</tbody> | ||
</table> | ||
<div class="legend"> | ||
<strong>Table 1</strong>: Criteria for bipolar disease I. | ||
</div> | ||
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To specify a disease, it is preferable to use a term from a disease ontology such as Mondo. | ||
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### Exceptions | ||
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Many Mendelian diseases are characterized by a highly increased risk for certain diseases. For instance, individuals with Bardet-Biedl syndrome frequently have [Diabetes mellitus (HP:0000819)](https://hpo.jax.org/browse/term/HP:0000819){:target="\_blank"}. Frequently, this is the only information that is available in medical publications (e.g., it would be noted that a person with BBS has diabetes, but the manifestations and time course of diabetes in that individual are not specified). For this reason, the | ||
HPO has a number of "diagnostic" terms. | ||
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Also, in some cases, a medical history of a disease can be considered to be a phenotypic feature. For instance, infections following live vaccinations such as [BCGosis HP:0020087](https://hpo.jax.org/browse/term/HP:0020087){:target="\_blank"} can be manifestations of some inborn errors of immunity. | ||
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## Pie rule | ||
The Pie Rule (also known as the Brie rule) states: | ||
<div class="highlight-box"> | ||
The set of child terms of a given term should robustly cover the specific subclasses of the parent term, such that a parent term could always be replaced with a more specific child term. | ||
</div> | ||
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<figure markdown> | ||
![Phenopacket Schema](../img/pie.png){ width="200" } | ||
<figcaption class="left-align"><b>Pie rule</b>. | ||
If a term has one or more subclasses, then ideally the subclasses should be about the same "size" and completely cover the pie. | ||
</figcaption> | ||
</figure> | ||
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Consider, for instance, the term [Abnormal cardiac septum morphology (HP:0001671)](https://hpo.jax.org/browse/term/HP:0001671){:target="\_blank"}. | ||
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<figure markdown> | ||
![Phenopacket Schema](../img/septum.png){ width="300" } | ||
<figcaption class="left-align"><b>Abnormal cardiac septum morphology</b>. | ||
</figcaption> | ||
</figure> | ||
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Abnormal cardiac septum morphology has three subterms. On the HPO website, if you hover over the gray bars, you can see the number of descendent terms for each of them. | ||
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- [Abnormal ventricular septum morphology (HP:0010438)](https://hpo.jax.org/browse/term/HP:0010438){:target="\_blank"}: 14 subterms, including specific terms such as [Perimembranous ventricular septal defect HP:0011682](https://hpo.jax.org/browse/term/HP:0011682){:target="\_blank"}. | ||
- [Abnormal atrial septum morphology (HP:0011994)](https://hpo.jax.org/browse/term/HP:0011994){:target="\_blank"}: 8 subterms, including specific terms such as [Secundum atrial septal defect (HP:0001684)](https://hpo.jax.org/browse/term/HP:0001684){:target="\_blank"} | ||
- [Atrioventricular canal defect (HP:0006695)](https://hpo.jax.org/browse/term/HP:0006695){:target="\_blank"}: 6 subterms, including specific terms such as [Complete atrioventricular canal defect (HP:0001674)](https://hpo.jax.org/browse/term/HP:0001674){:target="\_blank"}. | ||
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Thus, here the HPO attempts to cover all of the specific kinds of *Abnormal cardiac septum morphology*. | ||
The three main subclasses are covered and all three have roughly the same number of terms. It would be a mistake, in contrast, if [Abnormal cardiac septum morphology (HP:0001671)](https://hpo.jax.org/browse/term/HP:0001671){:target="\_blank"} had the subclasses | ||
[Abnormal ventricular septum morphology (HP:0010438)](https://hpo.jax.org/browse/term/HP:0010438){:target="\_blank"}, [Abnormal atrial septum morphology (HP:0011994)](https://hpo.jax.org/browse/term/HP:0011994){:target="\_blank"}, and then [Complete atrioventricular canal defect (HP:0001674)](https://hpo.jax.org/browse/term/HP:0001674){:target="\_blank"}, [Partial atrioventricular canal defect (HP:0011577)](https://hpo.jax.org/browse/term/HP:0011577){:target="\_blank"}, and so on for the other four child terms of [Atrioventricular canal defect (HP:0006695)](https://hpo.jax.org/browse/term/HP:0006695){:target="\_blank"}, because the former two terms have a different granularity (they are grouping terms) than the latter (they are specific terms). | ||
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## The 5 o-clock rule | ||
This rule states that | ||
<div class="highlight-box"> | ||
Terms should be easy to find by walking down the hierarchy. That is, a clinician should be able to find the right term at 5:00 pm on a Friday after a long work week. | ||
</div> | ||
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It is of course hard to precisely define this rule, but basically the hierarchy of the HPO should reflect, to the extent possible, current clinical thinking and not ontological abstractions. | ||
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# Why are these rules important? | ||
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Consider the following (made-up) example. At first glance, it may appear correct - after all, patients with depressed mood may lose weight, be tearful, and have sleep disturbances. | ||
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<figure markdown> | ||
![Phenopacket Schema](../img/depressedmood.png){ width="400" } | ||
<figcaption class="left-align"><b>Example: depressed mood</b>. | ||
</figcaption> | ||
</figure> | ||
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However, note that these are not actually **subclass** relations. Instead, they are **has-phenotype** relations in the sense that a patient with depressed mood often has the three phenotypic features in question. However, not every patient with sleep distrubance has depressed mood. Other causes include | ||
sleep apnea, restless Legs Syndrome, narcolepsy, chronic pain, certain medications, caffeine, alcohol, environmental factors such as loud noises, thyroid conditions, parkinson disease, and many others. | ||
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Therefore, if we encoded this relation in the HPO (which only uses subclass relations), then HPO-aware computer programs would falsely conclude that every patient with any one of the above diseases who happened to have a sleep disturbance also has depressed mood. While this may be true for some, it is not true in general, and this would lead to erroneous results. | ||
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The structure of the HPO is designed to follow the above rules to ensure accuracy of computational algorithms that use HPO. | ||
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