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fix uncertain insertion #10

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merged 6 commits into from
Oct 16, 2024
Merged

fix uncertain insertion #10

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ed67196
fix!: fix dna ins/delins unknown repeat notation
nokara26 Sep 24, 2024
c2e025d
fix!: fix rna ins unknown repeat notation
nokara26 Sep 24, 2024
e11455b
fix!: fix protein ins unknown repeat notation
nokara26 Sep 25, 2024
b551792
fix: add unknown repeat repairer
nokara26 Oct 15, 2024
4a0f788
feat: support indel unknown insertion and ins-format
nokara26 Oct 16, 2024
36d828d
chore: Prepare for next development iteration (0.5.0-SNAPSHOT)
nokara26 Oct 16, 2024
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2 changes: 1 addition & 1 deletion project.clj
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Original file line number Diff line number Diff line change
@@ -1,4 +1,4 @@
(defproject clj-hgvs "0.4.7"
(defproject clj-hgvs "0.5.0-SNAPSHOT"
:description "Clojure(Script) library for handling HGVS"
:url "https://github.com/chrovis/clj-hgvs"
:license {:name "Apache License, Version 2.0"
Expand Down
132 changes: 94 additions & 38 deletions src/clj_hgvs/mutation.cljc
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Expand Up @@ -430,7 +430,7 @@
;;; g.122_123ins123_234inv (TODO)
;;; g.122_123ins213_234invinsAins123_211inv (TODO)
;;; g.549_550insN
;;; g.1134_1135ins(100)
;;; g.1134_1135insN[100]
;;; g.?_?insNC_000023.10:(12345_23456)_(34567_45678)

(defrecord DNAInsertion [coord-start coord-end alt]
Expand All @@ -445,10 +445,10 @@
(string? alt) (case ins-format
:auto (if (and (every? #(= % \N) alt)
(>= (count alt) 10))
(str "(" (count alt) ")")
(str "N[" (count alt) "]")
alt)
:bases alt
:count (str "(" (count alt) ")"))
:count (str "N[" (count alt) "]"))
(map? alt) [(:transcript alt)
":"
(coord/format (:coord-start alt))
Expand Down Expand Up @@ -478,7 +478,7 @@
(defn- parse-dna-insertion-alt
[s kind]
(or (re-matches #"[A-Z]+" s)
(some-> (re-matches #"\((\d+)\)" s)
(some-> (re-matches #"N\[(\d+)\]" s)
(second)
(intl/parse-long)
(repeat "N")
Expand Down Expand Up @@ -624,20 +624,28 @@
;;; e.g. g.6775delinsGA
;;; g.6775delTinsGA
;;; c.145_147delinsTGG
;;; c.145_147delinsN[10]
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Though only a reference page of DNA deletion-insertion have an example of uncertain insertion, theoretically, RNA deletion-insertion and protein deletion-insertion can also have the uncertain insertion. Mutalyzer supports delinsn, e.g. https://mutalyzer.nl/normalizer/NM_004006.2:r.2623_2803delinsn. Implementation of the uncertain insertion for only DNA deletion-insertion seems incomplete 🤔


(defrecord DNAIndel [coord-start coord-end ref alt]
Mutation
(format [this] (format this nil))
(format [this {:keys [show-bases?] :or {show-bases? false}}]
(format [this {:keys [show-bases? ins-format] :or {show-bases? false ins-format :auto}}]
(apply str (flatten [(coord/format coord-start)
(if (and coord-end
(or (not (coord/comparable-coordinates? coord-start coord-end))
(neg? (compare coord-start coord-end))))
(when (and coord-end
(or (not (coord/comparable-coordinates? coord-start coord-end))
(neg? (compare coord-start coord-end))))
["_" (coord/format coord-end)])
"del"
(if show-bases? ref)
(when show-bases? ref)
"ins"
alt])))
(when (string? alt)
(case ins-format
:auto (if (and (every? #(= % \N) alt)
(>= (count alt) 10))
(str "N[" (count alt) "]")
alt)
:bases alt
:count (str "N[" (count alt) "]")))])))
(plain [this]
(into {:mutation "dna-indel"} (plain-coords this)))

Expand All @@ -663,6 +671,15 @@
:clj-hgvs.mutation.dna-indel/ref
:clj-hgvs.mutation.dna-indel/alt])))

(defn- parse-dna-indel-alt
[s]
(or (re-matches #"[A-Z]+" s)
(some-> (re-matches #"N\[(\d+)\]" s)
(second)
(intl/parse-long)
(repeat "N")
(#(apply str %)))))

(defn dna-indel
"Constructor of DNAIndel. Throws an exception if any input is illegal."
[coord-start coord-end ref alt]
Expand All @@ -673,13 +690,16 @@
(DNAIndel. coord-start coord-end ref alt))

(def ^:private dna-indel-re
#"([\d\-\+\*\?]+)(?:_([\d\-\+\*\?]+))?del([A-Z]+)?ins([A-Z]+)")
#"([\d\-\+\*\?]+)(?:_([\d\-\+\*\?]+))?del([A-Z]+)?ins(N\[\d+\]|[A-Z]+)")

(defn parse-dna-indel
[s kind]
(let [[_ coord-s coord-e ref alt] (re-matches dna-indel-re s)
parse-coord (coord-parser kind)]
(dna-indel (parse-coord coord-s) (some-> coord-e parse-coord) ref alt)))
(dna-indel (parse-coord coord-s)
(some-> coord-e parse-coord)
ref
(parse-dna-indel-alt alt))))

(defmethod restore "dna-indel"
[m]
Expand Down Expand Up @@ -1036,20 +1056,25 @@
;;; RNA - insertion
;;;
;;; e.g. r.756_757insacu
;;; r.431_432ins(5)
;;; r.431_432insn[5]
;;; r.123_124insL37425.1:23_361

(defrecord RNAInsertion [coord-start coord-end alt]
Mutation
(format [this] (format this nil))
(format [this _]
(format [this {:keys [ins-format] :or {ins-format :auto}}]
(str (coord/format coord-start)
"_"
(coord/format coord-end)
"ins"
(cond
(map? alt) (str (:genbank alt) ":" (:coord-start alt) "_" (:coord-end alt))
(re-matches #"n{2,}" alt) (str "(" (count alt) ")")
(re-matches #"n{2,}" alt) (case ins-format
:auto (if (>= (count alt) 10)
(str "n[" (count alt) "]")
alt)
:bases alt
:count (str "n[" (count alt) "]"))
:else alt)))
(plain [this]
(into {:mutation "rna-insertion"} (plain-coords this))))
Expand All @@ -1074,9 +1099,9 @@

(defn- parse-rna-alt-n
[s]
(if-let [n (some-> (re-find #"\((\d)\)" s)
second
intl/parse-long)]
(when-let [n (some-> (re-find #"n\[(\d+)\]" s)
second
intl/parse-long)]
(apply str (repeat n "n"))))

(def ^:private genbank-re
Expand All @@ -1098,8 +1123,8 @@
(rna-insertion (coord/parse-rna-coordinate coord-s)
(some-> coord-e coord/parse-rna-coordinate)
(cond
(re-find #"n\[\d+\]" alt) (parse-rna-alt-n alt)
(re-find #"[a-z]+" alt) alt
(re-find #"\(\d\)" alt) (parse-rna-alt-n alt)
:else (parse-rna-alt-genbank alt)))))

(defmethod restore "rna-insertion"
Expand Down Expand Up @@ -1218,20 +1243,28 @@
;;; e.g. r.775delinsga
;;; r.775deluinsga
;;; r.775_777delinsc
;;; r.775_777delinsn[10]

(defrecord RNAIndel [coord-start coord-end ref alt]
Mutation
(format [this] (format this nil))
(format [this {:keys [show-bases?] :or {show-bases? false}}]
(format [this {:keys [show-bases? ins-format] :or {show-bases? false ins-format :auto}}]
(str (coord/format coord-start)
(if (and coord-end
(or (not (coord/comparable-coordinates? coord-start coord-end))
(neg? (compare coord-start coord-end))))
(when (and coord-end
(or (not (coord/comparable-coordinates? coord-start coord-end))
(neg? (compare coord-start coord-end))))
(str "_" (coord/format coord-end)))
"del"
(if show-bases? ref)
(when show-bases? ref)
"ins"
alt))
(if (re-matches #"n{2,}" alt)
(case ins-format
:auto (if (>= (count alt) 10)
(str "n[" (count alt) "]")
alt)
:bases alt
:count (str "n[" (count alt) "]"))
alt)))
(plain [this]
(into {:mutation "rna-indel"} (plain-coords this)))

Expand Down Expand Up @@ -1267,15 +1300,17 @@
(RNAIndel. coord-start coord-end ref alt))

(def ^:private rna-indel-re
#"([\d\-\+\*]+)(?:_([\d\-\+\*]+))?del([a-z]+)?ins([a-z]+)")
#"([\d\-\+\*]+)(?:_([\d\-\+\*]+))?del([a-z]+)?ins([a-z\d\[\]]+)")

(defn parse-rna-indel
[s]
(let [[_ coord-s coord-e ref alt] (re-matches rna-indel-re s)]
(rna-indel (coord/parse-rna-coordinate coord-s)
(some-> coord-e coord/parse-rna-coordinate)
ref
alt)))
(if (re-find #"n\[\d+\]" alt)
(parse-rna-alt-n alt)
alt))))

(defmethod restore "rna-indel"
[m]
Expand Down Expand Up @@ -1724,12 +1759,12 @@
;;; Protein - insertion
;;;
;;; e.g. Lys23_Leu24insArgSerGln
;;; Arg78_Gly79ins23
;;; Arg78_Gly79insX[23]

(defrecord ProteinInsertion [ref-start coord-start ref-end coord-end alts]
Mutation
(format [this] (format this nil))
(format [this {:keys [amino-acid-format] :or {amino-acid-format :long}}]
(format [this {:keys [amino-acid-format ins-format] :or {amino-acid-format :long ins-format :auto}}]
(apply str (flatten [(cond-> ref-start
(= amino-acid-format :short) ->short-amino-acid)
(coord/format coord-start)
Expand All @@ -1739,7 +1774,14 @@
(coord/format coord-end)
"ins"
(if (every? #(= % "Xaa") alts)
(count alts)
(let [alts (cond->> alts
(= amino-acid-format :short) (map ->short-amino-acid))]
(case ins-format
:auto (if (>= (count alts) 10)
(str "X[" (count alts) "]")
alts)
:amino-acids alts
:count (str "X[" (count alts) "]")))
(cond->> alts
(= amino-acid-format :short) (map ->short-amino-acid)))])))
(plain [this]
Expand Down Expand Up @@ -1770,10 +1812,14 @@
[s]
(condp re-matches s
#"([A-Z*]([a-z]{2})?)+" (mapv ->long-amino-acid (re-seq #"[A-Z*](?:[a-z]{2})?" s))
#"\d+" (vec (repeat (intl/parse-long s) "Xaa"))))
#"X\[\d+\]" (-> (re-find #"X\[(\d+)\]" s)
second
intl/parse-long
(repeat "Xaa")
vec)))

(def ^:private protein-insertion-re
#"([A-Z](?:[a-z]{2})?)(\d+)_([A-Z](?:[a-z]{2})?)(\d+)ins([\da-zA-Z*]+)")
#"([A-Z](?:[a-z]{2})?)(\d+)_([A-Z](?:[a-z]{2})?)(\d+)ins([\da-zA-Z*\[\]]+)")

(defn parse-protein-insertion
[s]
Expand All @@ -1793,22 +1839,32 @@
;;;
;;; e.g. Cys28delinsTrpVal
;;; Cys28_Lys29delinsTrp
;;; Cys28_Lys29delinsX[10]

(defrecord ProteinIndel [ref-start coord-start ref-end coord-end alts]
Mutation
(format [this] (format this nil))
(format [this {:keys [amino-acid-format] :or {amino-acid-format :long}}]
(format [this {:keys [amino-acid-format ins-format] :or {amino-acid-format :long ins-format :auto}}]
(apply str (flatten [(cond-> ref-start
(= amino-acid-format :short) ->short-amino-acid)
(coord/format coord-start)
(if (should-show-end? ref-start coord-start ref-end coord-end)
(when (should-show-end? ref-start coord-start ref-end coord-end)
["_"
(cond-> ref-end
(= amino-acid-format :short) ->short-amino-acid)
(coord/format coord-end)])
"delins"
(cond->> alts
(= amino-acid-format :short) (map ->short-amino-acid))])))
(if (every? #(= % "Xaa") alts)
(let [alts (cond->> alts
(= amino-acid-format :short) (map ->short-amino-acid))]
(case ins-format
:auto (if (>= (count alts) 10)
(str "X[" (count alts) "]")
alts)
:amino-acids alts
:count (str "X[" (count alts) "]")))
(cond->> alts
(= amino-acid-format :short) (map ->short-amino-acid)))])))
(plain [this]
(into {:mutation "protein-indel"} (plain-coords this))))

Expand All @@ -1835,7 +1891,7 @@
(ProteinIndel. ref-start coord-start ref-end coord-end alts))

(def ^:private protein-indel-re
#"([A-Z](?:[a-z]{2})?)(\d+)(?:_([A-Z](?:[a-z]{2})?)(\d+))?delins([A-Z*][a-zA-Z*]*)?")
#"([A-Z](?:[a-z]{2})?)(\d+)(?:_([A-Z](?:[a-z]{2})?)(\d+))?delins([A-Z*][a-zA-Z*\[\]\d]*)?")

(defn parse-protein-indel
[s]
Expand All @@ -1844,7 +1900,7 @@
(coord/parse-protein-coordinate coord-s)
(->long-amino-acid ref-e)
(some-> coord-e coord/parse-protein-coordinate)
(mapv ->long-amino-acid (some->> alts (re-seq #"[A-Z*](?:[a-z]{2})?"))))))
(mapv ->long-amino-acid (some->> alts parse-protein-insertion-alts)))))

(defmethod restore "protein-indel"
[m]
Expand Down
15 changes: 15 additions & 0 deletions src/clj_hgvs/repairer.cljc
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Expand Up @@ -156,6 +156,20 @@
(string/replace s #"del\d+ins" "delins")
s))

;; g.1134_1135ins(100) -> g.1134_1135insN[100]
;; r.431_432ins(5) -> r.431_432insn[5]
;; p.R78_G79ins23 -> p.R78_G79insX[23]
(defn ^:no-doc replace-uncertain-bases
[s kind]
(case kind
(:genome :mitochondria :coding-dna :non-coding-dna :circular-dna)
(string/replace s #"ins\((\d+)\)$" "insN[$1]")
(:rna)
(string/replace s #"ins\((\d+)\)$" "insn[$1]")
(:protein)
(string/replace s #"ins(\d+)$" "insX[$1]")
s))

;; c.112GAT(14) -> c.112GAT[14]
(defn ^:no-doc replace-repeated-seqs-parens1
[s kind]
Expand Down Expand Up @@ -318,6 +332,7 @@
remove-alternative
remove-inv-bases
remove-del-count-from-delins
replace-uncertain-bases
replace-repeated-seqs-parens1
replace-repeated-seqs-parens2
remove-genomic-bases-from-protein
Expand Down
5 changes: 5 additions & 0 deletions test/clj_hgvs/core_test.cljc
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Original file line number Diff line number Diff line change
Expand Up @@ -332,6 +332,11 @@
;; remove-del-count-from-delins
"c.123_124del2insCTGA" "c.123_124delinsCTGA"

;; replace-uncertain-bases
"g.1134_1135ins(100)" "g.1134_1135insN[100]"
"r.431_432ins(5)" "r.431_432insn[5]"
"p.R78_G79ins23" "p.R78_G79insX[23]"

;; replace-repeated-seqs-parens1
"c.112GAT(14)" "c.112GAT[14]"

Expand Down
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