様々なデータベースを使ってヒトミトコンドリア変異のアノテーションを行う hmtnote

2019 6/11 データベース追記

　HmtNoteは、VCFファイルからヒトのミトコンドリアのバリアントにアノテーションを付けるためのPythonパッケージである。バリアントは、基本、相互参照、変動性、予測のサブセットにグループ化された幅広い情報を使用してアノテーションが付けられているので、ユーザーは関心のある特定のアノテーションを選択するか、またはそれらをすべて使用できる。アノテーションは、最近公開されたヒトミトコンドリア変異のデータベースであるHmtVarのデータを使用して実行される。これは、いくつかのオンラインリソースから情報を収集し、病原性予測を提供する。HmtNoteは、インターネット接続に頼ることなく、オフラインでバリアントにアノテーションを付けるために使用できるローカルアノテーションデータベースをダウンロードすることもできる。HmtNoteはフリーでオープンソースのパッケージで、PyPI（https://pypi.org/project/hmtnote）またはGitHub（https://github.com/robertopreste/HmtNote）からダウンロードしてインストールできる。

People of #bioinformatics, if you need to annotate human mitochondrial variants from VCF files please have a look at my new HmtNote #python python package! 😊 https://t.co/4GI9W2HYev https://t.co/NoArqXGX1r
— Roberto Preste (@robertopreste) April 11, 2019

マニュアル

インストール

ubuntu16.04のminiconda3-4.0.5環境でテストした。

依存

HmtNote only supports Python 3.

本体　Github

pip install hmtnote
export LC_ALL=C.UTF-8 && export LANG=C.UTF-8

> hmtnote --help

# hmtnote --help

Usage: hmtnote [OPTIONS] COMMAND [ARGS]...

Options:

--version Show the version and exit.

--help Show this message and exit.

Commands:

annotate Annotate a VCF file using data from HmtVar.

dump Download databases from HmtVar for offline annotation.

> hmtnote annotate --help

# hmtnote annotate --help

Usage: hmtnote annotate [OPTIONS] INPUT_VCF OUTPUT_VCF

Annotate a VCF file using data from HmtVar.

If neither --basic, --crossref, --variab nor --predict are provided, they

will all default to True, and the VCF will be annotated using all the

available information. If no internet connection is available, use the

--offline option to use the local database for annotation (you must have

previously downloaded it using the hmtnote dump command).

Options:

-b, --basic Annotate VCF using basic information (locus, pathogenicity,

etc.)

(default: False)

-c, --crossref Annotate VCF using cross-reference information (Clinvar and

dbSNP IDs, etc.)

(default: False)

-v, --variab Annotate VCF using variability information (nucleotide and

aminoacid

variability, allele frequencies) (default: False)

-p, --predict Annotate VCF using predictions information (from MutPred,

Panther, Polyphen

and other resources) (default: False)

-o, --offline Annotate VCF using previously downloaded databases (offline

mode)

(default: False)

--help Show this message and exit.

> hmtnote dump --help

# hmtnote dump --help

Usage: hmtnote dump [OPTIONS]

Download databases from HmtVar for offline annotation.

Options:

--help Show this message and exit.

実行方法

on the fly でHmtVarのデータベース（webページ, pubmed）を使ってミトコンドリア変異のアノテーションを行う。入力のvcfと出力のvcfをそれぞれ指定する。annotateコマンドでは４つのアノテーション、basic、cross-reference、variability、predictionsを全て行う。

hmtnote annotate input.vcf output_annotated.vcf

本番環境がオフラインの場合、前もってデータをダウンロードしてから実行する。

hmtnote dump

hmtnote annotate input.vcf annotated.vcf --offline
hmtnote annotate input.vcf annotated_variability.vcf --variab --offline

下にも載せましたが、どのようなデータベースやフィルタリング条件が使われているかはmanualを確認してください。

https://hmtnote.readthedocs.io/en/latest/usage.html

マニュアルより転載

basic

Locus: Locus to which the variant belongs
AaChange: Aminoacidic change determined
Pathogenicity: Pathogenicity predicted by HmtVar
DiseaseScore: Disease score calculated by HmtVar
HmtVar: HmtVar ID of the variant (can be used to view the related VariantCard on https://www.hmtvar.uniba.it/varCard/)

Cross-reference

Clinvar: Clinvar ID of the variant
dbSNP: dbSNP ID of the variant
OMIM: OMIM ID of the variant
MitomapAssociatedDiseases: Diseases associated to the variant according to Mitomap
MitomapSomaticMutations: Diseases associated to the variant according to Mitomap Somatic Mutations

Variability

NtVarH: Nucleotide variability of the position in healthy individuals
NtVarP: Nucleotide variability of the position in patient individuals
AaVarH: Aminoacid variability of the position in healthy individuals
AaVarP: Aminoacid variability of the position in patient individuals
AlleleFreqH: Allele frequency of the variant in healthy individuals overall
AlleleFreqP: Allele frequency of the variant in patient individuals overall
AlleleFreqH_AF: Allele frequency of the variant in healthy individuals from Africa
AlleleFreqP_AF: Allele frequency of the variant in patient individuals from Africa
AlleleFreqH_AM: Allele frequency of the variant in healthy individuals from America
AlleleFreqP_AM: Allele frequency of the variant in patient individuals from America
AlleleFreqH_AS: Allele frequency of the variant in healthy individuals from Asia
AlleleFreqP_AS: Allele frequency of the variant in patient individuals from Asia
AlleleFreqH_EU: Allele frequency of the variant in healthy individuals from Europe
AlleleFreqP_EU: Allele frequency of the variant in patient individuals from Europe
AlleleFreqH_OC: Allele frequency of the variant in healthy individuals from Oceania
AlleleFreqP_OC: Allele frequency of the variant in patient individuals from Oceania

Predictions

MutPred_Prediction: Pathogenicity prediction offered by MutPred
MutPred_Probability: Confidence of the pathogenicity prediction offered by MutPred
Panther_Prediction: Pathogenicity prediction offered by Panther
Panther_Probability: Confidence of the pathogenicity prediction offered by Panther
PhDSNP_Prediction: Pathogenicity prediction offered by PhD SNP
PhDSNP_Probability: Confidence of the pathogenicity prediction offered by PhD SNP
SNPsGO_Prediction: Pathogenicity prediction offered by SNPs & GO
SNPsGO_Probability: Confidence of the pathogenicity prediction offered by SNPs & GO
Polyphen2HumDiv_Prediction: Pathogenicity prediction offered by Polyphen2 HumDiv
Polyphen2HumDiv_Probability: Confidence of the pathogenicity prediction offered by Polyphen2 HumDiv
Polyphen2HumVar_Prediction: Pathogenicity prediction offered by Polyphen2 HumVar
Polyphen2HumVar_Probability: Confidence of the pathogenicity prediction offered by Polyphen2 HumVar