feat: implement SV type INS on the library level (#146)

src/api/annonars/client.ts

@@ -154,11 +154,14 @@ export class AnnonarsClient {
     pageSize: number = 1000,
     minOverlap: number = 0.1
   ): Promise<ClinvarSvQueryResponse> {
-    const { svType, genomeBuild, chrom, start, stop } = strucvar
-    if (svType === 'BND') {
-      // We don't properly support ClinVar BNDs (and there will be few..)
+    // First, check if we can handle the SV type.
+    const { svType } = strucvar
+    if (svType === 'BND' || svType === 'INS') {
+      // We don't properly support ClinVar INS/BNDs (and there will be few..)
       return { records: [] }
     }
+    // Then, extract coordinates of linear strucvar.
+    const { genomeBuild, chrom, start, stop } = strucvar
 
     const url =
       `${this.apiBaseUrl}/clinvar-sv/query?genomeRelease=${genomeBuild}&` +

src/api/mehari/client.ts

@@ -59,10 +59,18 @@ export class MehariClient {
    * @throws Error if the API request fails.
    */
   async retrieveStrucvarsCsq(strucvar: Strucvar): Promise<StrucvarResult> {
-    const { genomeBuild, chrom, start, stop, svType } = strucvar
-    const url =
-      `${this.apiBaseUrl}/strucvars/csq?genome_release=${genomeBuild}&` +
-      `chromosome=${chrom}&start=${start}&stop=${stop}&sv_type=${svType}`
+    let url: string
+    const { svType, genomeBuild, chrom, start } = strucvar
+    if (svType === 'BND' || svType === 'INS') {
+      url =
+        `${this.apiBaseUrl}/strucvars/csq?genome_release=${genomeBuild}&` +
+        `chromosome=${chrom}&start=${start}&stop=${start + 1}&sv_type=${svType}`
+    } else {
+      const { stop } = strucvar
+      url =
+        `${this.apiBaseUrl}/strucvars/csq?genome_release=${genomeBuild}&` +
+        `chromosome=${chrom}&start=${start}&stop=${stop}&sv_type=${svType}`
+    }
 
     const response = await fetch(url, {
       method: 'GET'

src/components/StrucvarClinvarCard/StrucvarClinvarCard.vue

@@ -38,8 +38,13 @@ const clinvarRange = computed<string>(() => {
     return ''
   }
   const release = props.strucvar.genomeBuild === 'grch37' ? 'GRCh37' : 'GRCh38'
-  const { chrom, start, stop } = props.strucvar
-  return `${release}:${chrom.replace('chr', '')}:${start}-${stop}`
+  const { svType, chrom, start } = props.strucvar
+  if (svType === 'BND' || svType === 'INS') {
+    return `${release}:${chrom.replace('chr', '')}:${start}-${start}`
+  } else {
+    const { stop } = props.strucvar
+    return `${release}:${chrom.replace('chr', '')}:${start}-${stop}`
+  }
 })
 
 const sortBy = ref<{ key: string; order: 'asc' | 'desc' }[]>([{ key: 'overlap', order: 'desc' }])

src/components/StrucvarToolsCard/StrucvarToolsCard.vue

@@ -9,24 +9,34 @@ const props = defineProps<{
   strucvar?: Strucvar
 }>()
 
+const svStop = (strucvar: Strucvar): number => {
+  return strucvar.svType === 'INS' || strucvar.svType === 'BND' ? strucvar.start + 1 : strucvar.stop
+}
+
 const ucscLinkout = computed((): string => {
   if (!props.strucvar) {
     return '#'
   }
   const db = props.strucvar?.genomeBuild === 'grch37' ? 'hg19' : 'hg38'
-  return (
-    `https://genome-euro.ucsc.edu/cgi-bin/hgTracks?db=${db}&position=` +
-    `${props.strucvar.chrom}:${props.strucvar.start}-` +
-    `${props.strucvar.stop}`
-  )
+  if (props.strucvar.svType === 'BND' || props.strucvar.svType === 'INS') {
+    return (
+      `https://genome-euro.ucsc.edu/cgi-bin/hgTracks?db=${db}&position=` +
+      `${props.strucvar.chrom}:${props.strucvar.start}-${svStop(props.strucvar)}`
+    )
+  } else {
+    return (
+      `https://genome-euro.ucsc.edu/cgi-bin/hgTracks?db=${db}&position=` +
+      `${props.strucvar.chrom}:${props.strucvar.start}-${svStop(props.strucvar)}`
+    )
+  }
 })
 
 const ensemblLinkout = computed((): string => {
   if (!props.strucvar) {
     return '#'
   }
-  const loc = `${props.strucvar.chrom}:${props.strucvar.start}-${props.strucvar.stop}`
-  if (props.strucvar?.genomeBuild === 'grch37') {
+  const loc = `${props.strucvar.chrom}:${props.strucvar.start}-${svStop(props.strucvar)}`
+  if (props.strucvar.genomeBuild === 'grch37') {
     return `https://grch37.ensembl.org/Homo_sapiens/Location/View?r=${loc}`
   } else if (props.strucvar?.genomeBuild === 'grch38') {
     return `https://ensembl.org/Homo_sapiens/Location/View?r=${loc}`
@@ -39,9 +49,10 @@ const dgvLinkout = computed((): string => {
     return '#'
   }
   const db = props.strucvar?.genomeBuild === 'grch37' ? 'hg19' : 'hg38'
+
   return (
     `http://dgv.tcag.ca/gb2/gbrowse/dgv2_${db}/?name=${props.strucvar.chrom}:` +
-    `${props.strucvar.start}-${props.strucvar.stop};search=Search`
+    `${props.strucvar.start}-${svStop(props.strucvar)};search=Search`
   )
 })
 
@@ -52,7 +63,7 @@ const gnomadLinkout = computed((): string => {
   const dataset = props.strucvar?.genomeBuild === 'grch37' ? 'gnomad_r2_1' : 'gnomad_r3'
   return (
     `https://gnomad.broadinstitute.org/region/${props.strucvar.chrom}:` +
-    `${props.strucvar.start}-${props.strucvar.stop}?dataset=${dataset}`
+    `${props.strucvar.start}-${svStop(props.strucvar)}?dataset=${dataset}`
   )
 })
 
@@ -64,16 +75,16 @@ const varsomeLinkout = computed((): string => {
   const chrom = props.strucvar.chrom.startsWith('chr')
     ? props.strucvar.chrom
     : `chr${props.strucvar.chrom}`
-  return `https://varsome.com/cnv/${urlRelease}/${chrom}:${props.strucvar.start}:${props.strucvar.stop}:${props.strucvar.svType}`
+  return `https://varsome.com/cnv/${urlRelease}/${chrom}:${props.strucvar.start}:${svStop(props.strucvar)}:${props.strucvar.svType}`
 })
 
 const franklinLinkout = computed((): string => {
   if (!props.strucvar) {
     return '#'
   }
-  const { chrom, start, stop, svType } = props.strucvar
+  const { chrom, start, svType } = props.strucvar
   const urlRelease = props.strucvar?.genomeBuild === 'grch37' ? 'hg19' : 'hg38'
-  return `https://franklin.genoox.com/clinical-db/variant/sv/chr${chrom}-${start}-${stop}-${svType}-${urlRelease}`
+  return `https://franklin.genoox.com/clinical-db/variant/sv/chr${chrom}-${start}-${svStop(props.strucvar)}-${svType}-${urlRelease}`
 })
 
 const jumpToLocus = async () => {
@@ -82,7 +93,7 @@ const jumpToLocus = async () => {
     : `chr${props.strucvar?.chrom}`
   // NB: we allow the call to fetch here as it goes to local IGV.
   await fetch(
-    `http://127.0.0.1:60151/goto?locus=${chrPrefixed}:${props.strucvar?.start}-${props.strucvar?.stop}`
+    `http://127.0.0.1:60151/goto?locus=${chrPrefixed}:${props.strucvar?.start}-${svStop(props.strucvar!)}`
   ).catch((e) => {
     const msg = "Couldn't connect to IGV. Please make sure IGV is running and try again."
     alert(msg)

src/lib/genomicVars.ts

@@ -66,7 +66,7 @@ export const REGEX_CNV_HYPHEN =
 export type CnvType = 'DEL' | 'DUP'
 
 /** Currently supported SV types. */
-export type SvType = CnvType | 'INV' | 'BND'
+export type SvType = CnvType | 'INV' | 'INS' | 'BND'
 
 /** Interface for regex groups when parsing with `REGEX_CNV_COLON` or `REGEX_CNV_HYPHEN`. */
 export interface RegexCnvGroups {
@@ -414,6 +414,92 @@ export enum StrandOrientation {
   NOT_APPLICABLE = 'NtoN'
 }
 
+/**
+ * Interface that describes a insertion strucvar.
+ */
+export interface InsertionStrucvar {
+  /** The type of the SV. */
+  svType: 'INS'
+  /** The genome build. */
+  genomeBuild: GenomeBuild
+  /**
+   * Canonical chromomsome name "1", .., "22", "X", "Y", "MT"
+   * **without** `chr` prefix.
+   */
+  chrom: string
+  /** The 1-based position. */
+  start: number
+  /** The inserted sequence. */
+  insSeq?: string
+  /** The length of the inserted sequence. */
+  insLen?: number
+  /** The user-facing representation. */
+  userRepr: string
+}
+
+/**
+ * Implementation of the `InsertionStrucvar` interface.
+ */
+export class InsertionStrucvarImpl implements InsertionStrucvar {
+  svType: 'INS'
+  genomeBuild: GenomeBuild
+  chrom: string
+  start: number
+  insSeq?: string
+  insLen?: number
+  userRepr: string
+
+  constructor(
+    genomeBuild: GenomeBuild,
+    chrom: string,
+    start: number,
+    insSeq?: string,
+    insLen?: number,
+    userRepr?: string
+  ) {
+    this.svType = 'INS'
+    this.genomeBuild = genomeBuild
+    this.chrom = chrom
+    this.start = start
+    this.insSeq = insSeq
+    this.insLen = insLen
+    let tmp = `${this.svType}-${this.genomeBuild}-${this.chrom}-${this.start}`
+    if (insSeq !== undefined) {
+      tmp += `-${insSeq}`
+    } else if (insLen !== undefined) {
+      tmp += `-${insLen}`
+    }
+    this.userRepr = userRepr ?? tmp
+  }
+
+  /** Return the "object name" to be used in the API to the backend etc. */
+  toName(): string {
+    let tmp = `${this.svType}-${this.genomeBuild}-${this.chrom}-${this.start}`
+    if (this.insSeq !== undefined) {
+      tmp += `-${this.insSeq}`
+    } else if (this.insLen !== undefined) {
+      tmp += `-${this.insLen}`
+    }
+    return tmp
+  }
+}
+
+/**
+ * Construct a `InsertionStrucvarImpl` from a `InsertionStrucvar`.
+ */
+export function insertionStrucvarImplFromInsertionStrucvar(
+  ins: InsertionStrucvar
+): InsertionStrucvarImpl {
+  return new InsertionStrucvarImpl(
+    ins.genomeBuild,
+    ins.chrom,
+    ins.start,
+    ins.insSeq,
+    ins.insLen,
+    ins.userRepr
+  )
+}
+
 /**
  * Interface that describes a breakend.
  */
@@ -501,7 +587,7 @@ export function breakendStrucvarImplFromBreakendStrucvar(
 }
 
 /** All supported structural variant types. */
-export type Strucvar = LinearStrucvar | BreakendStrucvar
+export type Strucvar = LinearStrucvar | InsertionStrucvar | BreakendStrucvar
 
 /**
  * Attempt parsing of a colon/hyphen-separated structural variant.