Variant Annotation Software Package (VASP)

Nisar Ahmad2 , Abaseen Aziz Zakhilwal1 , Sirajulhaq 1 , Ashfaq Hussain1

1
Department of Electrical and Electronics Engineering and Technology
University of Engineering and Technology Lahore, KSK Campus
Email:2 [email protected]

Abstract—VASP(Variant Annotation Software Package) is a (nsSNVs), most studies focus on whether these nsSNVs affect
software package for the analysis of genome sequencing data. The protein function. Computational studies show that the impact
accuracy of the the analysis of genome show that select the VASP of nsSNVs on protein function reflects sequence homology
for analysis and collection of data about diffrent genom diseases
are important. So this package is specially designed to study these and structural information and predict the impact through
variant annotation which are beneficial for both students and statistical methods, machine learning techniques, or models of
researchers. This GUI based software tool installation package protein evolution. Here, we review impact prediction methods
is made by using shell scripting and zenity which is able to and discuss their underlying principles, their advantages and
download and install 39 tools relating to the topic that can be limitations, and how they compare to and complement one
widely used in laboratory experiment. The instruction manual is
provided to guidance and help to its user. This software tool is another. Finally, we present current applications and future
free and both, the software and instrution manual is avaliable directions for these methods in biological research and medical
at: https://sourceforge.net/projects/vasp.sh/download genetics.
Index Terms—Variant Annotation, Annotation Tool, Genome, II. M ETHODS
GUI, Command line interface, Shell scripting LINUX A. Classification of SNP annotation
I. I NTRODUCTION 1) Gene based annotation
Gnomic information from surrounding gnomic elements
Variant annotation means the analysis of genome sequenc- is among the most useful information for interpreting the
ing data. A crucial step in linking sequence variants with biological function of an observed variant. Information from
changes in phenotype is called variant annotation. The an- a known gene is used as a reference to indicate whether
notation step in the analysis of a genome sequencing study the observed variant resides in or near a gene and if it
must be considered carefully, and a conscious choice made as has the potential to disrupt the protein sequence and its
to which transcript set and software are used for annotation. function. Gene based annotation is based on the fact that
Although there are many complications for variant annotation, non-synonymous mutations can alter the protein sequence and
we identify two major components: that splice site mutation may disrupt the transcript splicing
A. SNP(Single nucleotide polymorphisms) pattern.
frequently called SNPs (pronounced snips), are the most 2)Knowledge based annotation
common type of genetic variation among people. Each SNP Knowledge base annotation is done based on the information
represents a difference in a single DNA building block, called of gene attribute, protein function and its metabolism. In this
a nucleotide. For example, a SNP may replace the nucleotide type of annotation more emphasis is given to genetic variation
cytosine (C) with the nucleotide thymine (T) in a certain that disrupts the protein function domain, protein-protein
stretch of DNA.SNPs occur normally throughout a persons interaction and biological pathway. The non-coding region
DNA. They occur once in every 300 nucleotides on average, of genome contain many important regulatory elements
which means there are roughly 10 million SNPs in the human including promoter, enhancer and insulator, any kind of
genome. Most commonly, these variations are found in the change in this regulatory region can change the functionality
DNA between genes. They can act as biological markers, of that protein.[8] The mutation in DNA can change the RNA
helping scientists locate genes that are associated with disease. sequence and then influence the RNA secondary structure,
When SNPs occur within a gene or in a regulatory region near RNA binding protein recognition and miRNA binding
a gene. activity,.
B. SNV(Single Nucleotide Variants) 3) Functional annotation
Genome-wide association studies (GWAS) and whole-exome This method mainly identifies variant function based on
sequencing (WES) generate massive amounts of genomic the information whether the variant loci are in the known
variant information, and a major challenge is to identify functional region that harbor genomic or epigenomic signals.
which variations drive disease or contribute to phenotypic The function of non-coding variants are extensive in terms
traits. Because the majority of known disease-causing muta- of the affected genomic region and they involve in almost all
tions are exonic non-synonymous single nucleotide variations processes of gene regulation.
 TABLE I TABLE II
D ESCRIPTION OF T OOLS T OOLS W ORKING

Software Tools LINUX Published Free Verification Software Tools Install

Based after 2012 GenomeComb X
GenomeComb X X X X AnnoVAR X
AnnoVAR X X X X TransVAR X
TransVAR X X X X PayroTools ×
PayroTools X X X X SnapEff ×
SnapEff X X X X VarMatch ×
VarMatch X X X X Sofia ×
Sofia X X X X VarioTator ×
VarioTator X X X X AMF ×
AMF X X X X Taps-Varl ×
Taps-Varl X X X X Mendel,MD ×
Mendel,MD X X X X GemiNi ×
GemiNi X X X X SnpMeta ×
SnpMeta X X X X PyVar ×
PyVar X X X X VAX ×
VAX X X X X FEAtnoTator ×
FEAtnoTator X X X X AIRVF ×
AIRVF X X X X MultiRes ×
MultiRes X X X X TiSan ×
TiSan X X X X MyVariant ×
MyVariant X X X X VTools ×
VTools X X X X GSearch ×
GSearch X X X X SnpFilt ×
SnpFilt X X X X MAC ×
MAC X X X X PCGR ×
PCGR X X X X ConVasDB ×
ConVasDB X X X X VariBox ×
VariBox X X X X COVA ×
COVA X X X X VAT ×
VAT X X X X Pilon ×
Pilon X X X X ALG ×
ALG X X X X ReviSE Q ×
ReviSE Q X X X X Canary ×
Canary X X X X MaqGENE ×
MaqGENE X X X X PASsit ×
PASsit X X X X Variant ×
Variant X X X X VAGrENT ×
VAGrENT X X X X Choas ×
Choas X X X X Trams ×
Trams X X X X

III. R ESULTS AND D ISCUSSION

After addding all the Tools, Now we want to check that all
of the tools installable on operating system or not. The Table
II discusses this matter.
Fig. 1. Flow chart for Variant annotation
 ACCESSING AND OPERATING OF SHELL FILE V. AVAILABILITY AND REQUIRMENTS
Operaing System: Ubantu Os.
Name: VASP
URL:https://sourceforge.net/projects/vasp/download
License:GPL v3.0
Restriction: For education purpose only
size: 21 KB.
Version: 1.00
contact: [email protected]

VI. CONTRIBUTIONS
Nisar Ahmad and Abaseen Aziz zakhilawal worked in
together in shell scripting and participated in data collection.
Sirajulhaq worked in the preparation of report along with
Ashfaq hussain and online searches and preparation of manual.

R EFERENCES
[1] @articlewang2010annovar, title=ANNOVAR: functional annotation of
genetic variants from high-throughput sequencing data, author=Wang,
Kai and Li, Mingyao and Hakonarson, Hakon, journal=Nucleic acids
research, volume=38, number=16, pages=e164–e164, year=2010, pub-
lisher=Oxford University Press
[2] @articletomiyasu1953transvar, title=The Transvar directional coupler,
author=Tomiyasu, Kiyo and Cohn, Seymour B, journal=Proceedings
of the IRE, volume=41, number=7, pages=922–926, year=1953, pub-
lisher=IEEE
[3] @articleberciano2016nefl, title=NEFL N98S mutation: another cause
of dominant intermediate Charcot–Marie–Tooth disease with hetero-
geneous early-onset phenotype, author=Berciano, José and Peeters,
Kristien and Garcı́a, Antonio and López-Alburquerque, Tomás and
Gallardo, Elena and Hernández-Fabián, Arantxa and Pelayo-Negro,
Ana L and De Vriendt, Els and Infante, Jon and Jordanova, Albena,
journal=Journal of neurology, volume=263, number=2, pages=361–369,
year=2016, publisher=Springer
[4] @inproceedingsaalto1982advanced, title=Advanced High Performance
Guns with Refractory Liners for Erosion Resistance, author=Aalto,
PD and O’Hara, GP and D’Andrea, G, booktitle=Erosion Symposium,
ARRADCOM, Dover, NJ, 25-27 October 1982, pages=404, year=1982
[5] @articleteathanindex, title=INDEX-VOLUMES 31-40, au-
thor=TEATHAN, WHENARSENICS SAFERIN YOUR CUP OF,
publisher=HeinOnline
[6] @articlesun2016varmatch, title=VarMatch: robust matching of small
variant datasets using flexible scoring schemes, author=Sun, Chen
and Medvedev, Paul, journal=Bioinformatics, volume=33, number=9,
pages=1301–1308, year=2016, publisher=Oxford University Press
[7] @articledruker2001activity, title=Activity of a specific inhibitor of the
BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia
and acute lymphoblastic leukemia with the Philadelphia chromosome,
author=Druker, Brian J and Sawyers, Charles L and Kantarjian, Hagop
So this was the process to install VASP correct and efficient and Resta, Debra J and Reese, Sofia Fernandes and Ford, John M and
so these tools have very wide area of using now a days. and Capdeville, Renaud and Talpaz, Moshe, journal=New England Journal
it will be simple your work. of Medicine, volume=344, number=14, pages=1038–1042, year=2001,
publisher=Mass Medical Soc
[8] @articleschaafsma2016variotator, title=VariOtator, a software tool for
IV. CONCLUSION variation annotation with the Variation Ontology, author=Schaafsma,
Gerard CP and Vihinen, Mauno, journal=Human mutation, volume=37,
This package tools works for both students and researchers number=4, pages=344–349, year=2016, publisher=Wiley Online Library
in order to enhance their skills in bioinformatics and it serve [9] @articlemood1950introduction, title=Introduction to the Theory
as a good plateform to get familiar and work with new of Statistics., author=Mood, Alexander McFarlane, year=1950,
publisher=McGraw-hill
softwars as well. Morover, this package keeps on updating [10] @articleedelman1990extracranial, title=Extracranial carotid arteries:
as more tools are avaible to provide musch ease to its user. evaluation with” black blood” MR angiography., author=Edelman,
in case of any queries and suggestions, you can contact to Robert R and Mattle, Heinrich P and Wallner, Bernd and Bajakian,
R and Kleefield, J and Kent, C and Skillman, JJ and Mendel, JB and
Sirajulhq. Atkinson, DJ, journal=Radiology, volume=177, number=1, pages=45–
50, year=1990
[11] @articlewang2010annovar, title=ANNOVAR: functional annotation of [26] @articlesun2016varmatch, title=VarMatch: robust matching of small
genetic variants from high-throughput sequencing data, author=Wang, variant datasets using flexible scoring schemes, author=Sun, Chen
Kai and Li, Mingyao and Hakonarson, Hakon, journal=Nucleic acids and Medvedev, Paul, journal=Bioinformatics, volume=33, number=9,
research, volume=38, number=16, pages=e164–e164, year=2010, pub- pages=1301–1308, year=2016, publisher=Oxford University Press
lisher=Oxford University Press [27] @articledruker2001activity, title=Activity of a specific inhibitor of the
[12] @articletomiyasu1953transvar, title=The Transvar directional coupler, BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia
author=Tomiyasu, Kiyo and Cohn, Seymour B, journal=Proceedings and acute lymphoblastic leukemia with the Philadelphia chromosome,
of the IRE, volume=41, number=7, pages=922–926, year=1953, pub- author=Druker, Brian J and Sawyers, Charles L and Kantarjian, Hagop
lisher=IEEE and Resta, Debra J and Reese, Sofia Fernandes and Ford, John M and
[13] @articleberciano2016nefl, title=NEFL N98S mutation: another cause Capdeville, Renaud and Talpaz, Moshe, journal=New England Journal
of dominant intermediate Charcot–Marie–Tooth disease with hetero- of Medicine, volume=344, number=14, pages=1038–1042, year=2001,
geneous early-onset phenotype, author=Berciano, José and Peeters, publisher=Mass Medical Soc
Kristien and Garcı́a, Antonio and López-Alburquerque, Tomás and [28] @articleschaafsma2016variotator, title=VariOtator, a software tool for
Gallardo, Elena and Hernández-Fabián, Arantxa and Pelayo-Negro, variation annotation with the Variation Ontology, author=Schaafsma,
Ana L and De Vriendt, Els and Infante, Jon and Jordanova, Albena, Gerard CP and Vihinen, Mauno, journal=Human mutation, volume=37,
journal=Journal of neurology, volume=263, number=2, pages=361–369, number=4, pages=344–349, year=2016, publisher=Wiley Online Library
year=2016, publisher=Springer [29] @articlemood1950introduction, title=Introduction to the Theory
[14] @inproceedingsaalto1982advanced, title=Advanced High Performance of Statistics., author=Mood, Alexander McFarlane, year=1950,
Guns with Refractory Liners for Erosion Resistance, author=Aalto, publisher=McGraw-hill
PD and O’Hara, GP and D’Andrea, G, booktitle=Erosion Symposium, [30] @articleedelman1990extracranial, title=Extracranial carotid arteries:
ARRADCOM, Dover, NJ, 25-27 October 1982, pages=404, year=1982 evaluation with” black blood” MR angiography., author=Edelman,
[15] @articleteathanindex, title=INDEX-VOLUMES 31-40, au- Robert R and Mattle, Heinrich P and Wallner, Bernd and Bajakian,
thor=TEATHAN, WHENARSENICS SAFERIN YOUR CUP OF, R and Kleefield, J and Kent, C and Skillman, JJ and Mendel, JB and
publisher=HeinOnline Atkinson, DJ, journal=Radiology, volume=177, number=1, pages=45–
50, year=1990
[16] @articlesun2016varmatch, title=VarMatch: robust matching of small
[31] @articletomiyasu1953transvar, title=The Transvar directional coupler,
variant datasets using flexible scoring schemes, author=Sun, Chen
author=Tomiyasu, Kiyo and Cohn, Seymour B, journal=Proceedings
and Medvedev, Paul, journal=Bioinformatics, volume=33, number=9,
of the IRE, volume=41, number=7, pages=922–926, year=1953, pub-
pages=1301–1308, year=2016, publisher=Oxford University Press
lisher=IEEE
[17] @articledruker2001activity, title=Activity of a specific inhibitor of the [32] @articleberciano2016nefl, title=NEFL N98S mutation: another cause
BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia of dominant intermediate Charcot–Marie–Tooth disease with hetero-
and acute lymphoblastic leukemia with the Philadelphia chromosome, geneous early-onset phenotype, author=Berciano, José and Peeters,
author=Druker, Brian J and Sawyers, Charles L and Kantarjian, Hagop Kristien and Garcı́a, Antonio and López-Alburquerque, Tomás and
and Resta, Debra J and Reese, Sofia Fernandes and Ford, John M and Gallardo, Elena and Hernández-Fabián, Arantxa and Pelayo-Negro,
Capdeville, Renaud and Talpaz, Moshe, journal=New England Journal Ana L and De Vriendt, Els and Infante, Jon and Jordanova, Albena,
of Medicine, volume=344, number=14, pages=1038–1042, year=2001, journal=Journal of neurology, volume=263, number=2, pages=361–369,
publisher=Mass Medical Soc year=2016, publisher=Springer
[18] @articleschaafsma2016variotator, title=VariOtator, a software tool for [33] @inproceedingsaalto1982advanced, title=Advanced High Performance
variation annotation with the Variation Ontology, author=Schaafsma, Guns with Refractory Liners for Erosion Resistance, author=Aalto,
Gerard CP and Vihinen, Mauno, journal=Human mutation, volume=37, PD and O’Hara, GP and D’Andrea, G, booktitle=Erosion Symposium,
number=4, pages=344–349, year=2016, publisher=Wiley Online Library ARRADCOM, Dover, NJ, 25-27 October 1982, pages=404, year=1982
[19] @articlemood1950introduction, title=Introduction to the Theory [34] @articleteathanindex, title=INDEX-VOLUMES 31-40, au-
of Statistics., author=Mood, Alexander McFarlane, year=1950, thor=TEATHAN, WHENARSENICS SAFERIN YOUR CUP OF,
publisher=McGraw-hill publisher=HeinOnline
[20] @articleedelman1990extracranial, title=Extracranial carotid arteries: [35] @articlesun2016varmatch, title=VarMatch: robust matching of small
evaluation with” black blood” MR angiography., author=Edelman, variant datasets using flexible scoring schemes, author=Sun, Chen
Robert R and Mattle, Heinrich P and Wallner, Bernd and Bajakian, and Medvedev, Paul, journal=Bioinformatics, volume=33, number=9,
R and Kleefield, J and Kent, C and Skillman, JJ and Mendel, JB and pages=1301–1308, year=2016, publisher=Oxford University Press
Atkinson, DJ, journal=Radiology, volume=177, number=1, pages=45– [36] @articledruker2001activity, title=Activity of a specific inhibitor of the
50, year=1990 BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia
[21] @articlewang2010annovar, title=ANNOVAR: functional annotation of and acute lymphoblastic leukemia with the Philadelphia chromosome,
genetic variants from high-throughput sequencing data, author=Wang, author=Druker, Brian J and Sawyers, Charles L and Kantarjian, Hagop
Kai and Li, Mingyao and Hakonarson, Hakon, journal=Nucleic acids and Resta, Debra J and Reese, Sofia Fernandes and Ford, John M and
research, volume=38, number=16, pages=e164–e164, year=2010, pub- Capdeville, Renaud and Talpaz, Moshe, journal=New England Journal
lisher=Oxford University Press of Medicine, volume=344, number=14, pages=1038–1042, year=2001,
[22] @articletomiyasu1953transvar, title=The Transvar directional coupler, publisher=Mass Medical Soc
author=Tomiyasu, Kiyo and Cohn, Seymour B, journal=Proceedings [37] @articleschaafsma2016variotator, title=VariOtator, a software tool for
of the IRE, volume=41, number=7, pages=922–926, year=1953, pub- variation annotation with the Variation Ontology, author=Schaafsma,
lisher=IEEE Gerard CP and Vihinen, Mauno, journal=Human mutation, volume=37,
[23] @articleberciano2016nefl, title=NEFL N98S mutation: another cause number=4, pages=344–349, year=2016, publisher=Wiley Online Library
of dominant intermediate Charcot–Marie–Tooth disease with hetero- [38] @articlemood1950introduction, title=Introduction to the Theory
geneous early-onset phenotype, author=Berciano, José and Peeters, of Statistics., author=Mood, Alexander McFarlane, year=1950,
Kristien and Garcı́a, Antonio and López-Alburquerque, Tomás and publisher=McGraw-hill
Gallardo, Elena and Hernández-Fabián, Arantxa and Pelayo-Negro, [39] @articleedelman1990extracranial, title=Extracranial carotid arteries:
Ana L and De Vriendt, Els and Infante, Jon and Jordanova, Albena, evaluation with” black blood” MR angiography., author=Edelman,
journal=Journal of neurology, volume=263, number=2, pages=361–369, Robert R and Mattle, Heinrich P and Wallner, Bernd and Bajakian,
year=2016, publisher=Springer R and Kleefield, J and Kent, C and Skillman, JJ and Mendel, JB and
[24] @inproceedingsaalto1982advanced, title=Advanced High Performance Atkinson, DJ, journal=Radiology, volume=177, number=1, pages=45–
Guns with Refractory Liners for Erosion Resistance, author=Aalto, 50, year=1990
PD and O’Hara, GP and D’Andrea, G, booktitle=Erosion Symposium,
ARRADCOM, Dover, NJ, 25-27 October 1982, pages=404, year=1982
[25] @articleteathanindex, title=INDEX-VOLUMES 31-40, au-
thor=TEATHAN, WHENARSENICS SAFERIN YOUR CUP OF,
publisher=HeinOnline