feat: Update ACMG criteria for CNVs (#76) (#114)

backend/Pipfile

@@ -21,6 +21,8 @@ sqlalchemy = "*"
 tenacity = "*"
 uvicorn = "*"
 alembic = "*"
+requests = "*"
+types-requests = "*"
 
 [dev-packages]
 aiosqlite = "*"

backend/app/api/internal/endpoints/remote.py

@@ -1,6 +1,10 @@
 """Reverse proxies to external/remote services."""
 
+import ssl
+
 import httpx
+import requests
+import urllib3
 from fastapi import APIRouter, BackgroundTasks, Request, Response
 from fastapi.responses import JSONResponse, StreamingResponse
 from starlette.background import BackgroundTask
@@ -99,3 +103,45 @@ async def acmg(request: Request):
         if key.lower() in acmg_rating:
             acmg_rating[key.lower()] = value == 1
     return JSONResponse(acmg_rating)
+
+
+class CustomHttpAdapter(requests.adapters.HTTPAdapter):
+    # "Transport adapter" that allows us to use custom ssl_context.
+
+    def __init__(self, ssl_context=None, **kwargs):
+        self.ssl_context = ssl_context
+        super().__init__(**kwargs)
+
+    def init_poolmanager(self, connections, maxsize, block=False):
+        self.poolmanager = urllib3.poolmanager.PoolManager(
+            num_pools=connections, maxsize=maxsize, block=block, ssl_context=self.ssl_context
+        )
+
+
+def get_legacy_session():
+    ctx = ssl.create_default_context(ssl.Purpose.SERVER_AUTH)
+    ctx.options |= 0x4  # OP_LEGACY_SERVER_CONNECT
+    session = requests.session()
+    session.mount("https://", CustomHttpAdapter(ctx))
+    return session
+
+
+@router.get("/cnv/acmg/{path:path}")
+async def cnv_acmg(request: Request):
+    """Implement searching for ACMG classification for CNVs."""
+    query_params = request.query_params
+    chromosome = query_params.get("chromosome")
+    start = query_params.get("start")
+    end = query_params.get("end")
+    func = query_params.get("func")
+
+    if not chromosome or not start or not end or not func:
+        return Response(status_code=400, content="Missing query parameters")
+
+    backend_resp = get_legacy_session().post(
+        "https://phoenix.bgi.com/api/acit/jobs/",
+        data={"chromosome": chromosome, "start": start, "end": end, "func": func, "error": 0},
+    )
+    if backend_resp.status_code != 200:
+        return Response(status_code=backend_resp.status_code, content=backend_resp.content)
+    return JSONResponse(backend_resp.json())

frontend/src/components/SvDetails/AcmgRating.vue

@@ -0,0 +1,248 @@
+<script setup lang="ts">
+import { computed, onMounted, watch } from 'vue'
+
+import {
+  ACMG_CRITERIA_CNV_DEFS,
+  ACMG_CRITERIA_CNV_GAIN,
+  ACMG_CRITERIA_CNV_LOSS,
+  AcmgCriteriaCNVGain,
+  AcmgCriteriaCNVLoss,
+  Presence,
+  StateSourceCNV
+} from '@/lib/acmgCNV'
+import { StoreState } from '@/stores/misc'
+import { useSvAcmgRatingStore } from '@/stores/svAcmgRating'
+import type { SvRecord } from '@/stores/svInfo'
+
+const props = defineProps({
+  svRecord: Object as () => SvRecord | undefined
+})
+
+const acmgRatingStore = useSvAcmgRatingStore()
+
+const resetAcmgRating = () => {
+  if (!acmgRatingStore.acmgRating) {
+    return
+  }
+  acmgRatingStore.acmgRating.setUserToAutoCNV()
+}
+
+const calculateAcmgClass = computed((): string => {
+  if (!acmgRatingStore.acmgRating) {
+    return ''
+  }
+  const [acmgClass] = acmgRatingStore.acmgRating.getAcmgClass()
+  return acmgClass
+})
+
+const calculateAcmgScore = computed((): number => {
+  if (!acmgRatingStore.acmgRating) {
+    return 0
+  }
+  const [, score] = acmgRatingStore.acmgRating.getAcmgClass()
+  return score
+})
+
+watch(
+  () => [props.svRecord, acmgRatingStore.storeState],
+  async () => {
+    if (props.svRecord && acmgRatingStore.storeState === StoreState.Active) {
+      await acmgRatingStore.setAcmgRating(props.svRecord)
+    }
+  }
+)
+
+onMounted(async () => {
+  if (props.svRecord) {
+    await acmgRatingStore.setAcmgRating(props.svRecord)
+  }
+})
+
+const switchCriteria = (
+  criteria: AcmgCriteriaCNVLoss | AcmgCriteriaCNVGain,
+  presence: Presence
+) => {
+  if (presence === Presence.Present) {
+    acmgRatingStore.acmgRating.setPresence(StateSourceCNV.User, criteria, Presence.Absent)
+  } else {
+    acmgRatingStore.acmgRating.setPresence(StateSourceCNV.User, criteria, Presence.Present)
+  }
+
+  // Unset conflicting criteria
+  const conflictingEvidence = ACMG_CRITERIA_CNV_DEFS.get(criteria)?.conflictingEvidence
+  if (conflictingEvidence) {
+    for (const conflictingCriteria of conflictingEvidence) {
+      acmgRatingStore.acmgRating.setPresence(
+        StateSourceCNV.User,
+        conflictingCriteria,
+        Presence.Absent
+      )
+    }
+  }
+}
+</script>
+
+<template>
+  <div v-if="acmgRatingStore !== undefined">
+    <v-row>
+      <v-col cols="12" md="3"></v-col>
+      <v-col cols="12" md="6" class="section">
+        <div>
+          <div>
+            <h2 for="acmg-class"><strong>ACMG classification:</strong></h2>
+          </div>
+          <h1 title="Automatically determined ACMG class (Richards et al., 2015)">
+            {{ calculateAcmgClass }} with score: {{ calculateAcmgScore }}
+          </h1>
+          <router-link to="/acmg-docs" target="_blank">
+            Further documentation <v-icon>mdi-open-in-new</v-icon>
+          </router-link>
+        </div>
+        <div class="button-group">
+          <v-btn color="black" variant="outlined" @click="resetAcmgRating()"> Reset </v-btn>
+        </div>
+        <div>
+          <div>
+            <div>
+              <v-icon>mdi-information-outline</v-icon>
+              Select all fulfilled criteria to get the classification following Rooney Riggs
+              <i>et al.</i> (2020).
+            </div>
+          </div>
+        </div>
+      </v-col>
+      <v-col cols="12" md="3"></v-col>
+    </v-row>
+    <v-row>
+      <v-col class="d-flex flex-row flex-wrap">
+        <v-table>
+          <thead>
+            <tr>
+              <th width="20%">Evidence</th>
+              <th width="74%">Description</th>
+              <th width="3%">Suggested points</th>
+              <th width="3%">Max score</th>
+            </tr>
+          </thead>
+          <tbody v-if="props.svRecord?.svType === 'DEL'">
+            <tr v-for="criteria in ACMG_CRITERIA_CNV_LOSS" :key="criteria">
+              <td>
+                <v-switch
+                  :label="criteria"
+                  :model-value="
+                    acmgRatingStore.acmgRating.getCriteriaCNVState(criteria).presence ===
+                    Presence.Present
+                  "
+                  @update:model-value="
+                    switchCriteria(
+                      criteria,
+                      acmgRatingStore.acmgRating.getCriteriaCNVState(criteria).presence
+                    )
+                  "
+                  color="primary"
+                  hide-details="auto"
+                  density="compact"
+                  class="switch"
+                >
+                </v-switch>
+                <div v-if="ACMG_CRITERIA_CNV_DEFS.get(criteria)?.slider">
+                  <v-slider
+                    :model-value="
+                      acmgRatingStore.acmgRating.getCriteriaCNVState(criteria).score ?? 0
+                    "
+                    @update:model-value="
+                      acmgRatingStore.acmgRating.setScore(StateSourceCNV.User, criteria, $event)
+                    "
+                    :min="ACMG_CRITERIA_CNV_DEFS.get(criteria)?.minScore ?? 0"
+                    :max="ACMG_CRITERIA_CNV_DEFS.get(criteria)?.maxScore ?? 0"
+                    :step="0.05"
+                    thumb-label
+                    thumb-size="10"
+                    class="slider"
+                  />
+                </div>
+              </td>
+              <td>
+                {{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.hint }}
+                <br />
+                {{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.description ?? '' }}
+                <br />
+                Conflicting evidence:
+                {{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.conflictingEvidence }}
+              </td>
+              <td>{{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.defaultScore }}</td>
+              <td>{{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.maxScore }}</td>
+            </tr>
+          </tbody>
+          <tbody v-else-if="props.svRecord?.svType === 'DUP'">
+            <tr v-for="criteria in ACMG_CRITERIA_CNV_GAIN" :key="criteria">
+              <td>
+                <v-switch
+                  :label="criteria"
+                  :model-value="
+                    acmgRatingStore.acmgRating.getCriteriaCNVState(criteria).presence ===
+                    Presence.Present
+                  "
+                  @update:model-value="
+                    switchCriteria(
+                      criteria,
+                      acmgRatingStore.acmgRating.getCriteriaCNVState(criteria).presence
+                    )
+                  "
+                  color="primary"
+                  hide-details="auto"
+                  density="compact"
+                  class="switch"
+                >
+                </v-switch>
+                <div v-if="ACMG_CRITERIA_CNV_DEFS.get(criteria)?.slider">
+                  <v-slider
+                    :model-value="
+                      acmgRatingStore.acmgRating.getCriteriaCNVState(criteria).score ?? 0
+                    "
+                    @update:model-value="
+                      acmgRatingStore.acmgRating.setScore(StateSourceCNV.User, criteria, $event)
+                    "
+                    :min="ACMG_CRITERIA_CNV_DEFS.get(criteria)?.minScore ?? 0"
+                    :max="ACMG_CRITERIA_CNV_DEFS.get(criteria)?.maxScore ?? 1"
+                    :step="0.05"
+                    thumb-label
+                    thumb-size="10"
+                    class="slider"
+                  />
+                </div>
+              </td>
+              <td>
+                {{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.hint }}
+                <br />
+                {{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.description ?? '' }}
+                <br />
+                Conflicting evidence:
+                {{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.conflictingEvidence }}
+              </td>
+              <td>{{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.defaultScore }}</td>
+              <td>{{ ACMG_CRITERIA_CNV_DEFS.get(criteria)?.maxScore }}</td>
+            </tr>
+          </tbody>
+        </v-table>
+      </v-col>
+    </v-row>
+  </div>
+  <div v-else>
+    <div class="d-flex align-center justify-center" style="min-height: 300px">
+      <h3>Loading ACMG information</h3>
+      <v-progress-circular indeterminate></v-progress-circular>
+    </div>
+  </div>
+</template>
+
+<style scoped>
+.switch {
+  margin-left: 10px;
+  padding: 0px;
+}
+
+.slider {
+  margin-top: 10px;
+}
+</style>

frontend/src/components/SvDetails/SvGenes.vue

@@ -133,7 +133,7 @@ const onRowClicked = (event: Event, { item }: { item: GeneInfo }): void => {
 
 <template>
   <div>
-    <div>
+    <div style="max-width: 1300px">
       <v-data-table
         v-model:items-per-page="itemsPerPage"
         :headers="headers"