基因组水平的遗传负荷分析
Genomic Genetic Load Analysis   

jingyang Hu

Yunnan University

Thanks for your question. Acturally, We just counted the quantity for het or hom, and didn't take other factors into account.

Xin Liu

Institute of Zoology, Chinese Academy of Sciences

Dear Dr.Hu
I find in annotated vcf used by SNPEFF exist such pattern.
AC=7;AF=0.09;AN=84;BaseQRankSum=-0.21;DP=1121;ExcessHet=4.7214;FS=1.161;InbreedingCoeff=-0.0987;MLEAC=9;MLEAF=0.09;MQ=60;MQRankSum=0;QD=14.55;ReadPosRankSum=0.041;SOR=0.795;ANN=A|intron_variant|MODIFIER|EVM%20prediction%20Hic_asm_0.262|evm.TU.Hic_asm_0.262|transcript|evm.model.Hic_asm_0.262|protein_coding|10/10|c.1294+12546C>T||||||WARNING_TRANSCRIPT_NO_START_CODON GT:AD:DP:GQ:PL 0/0:18,0:18:48:0,48,720.
About "protein_coding|10/10|" this will be called het, but it is hom.

Regards,
XinLiu

黎 于

Thanks for your question.

This matrix was built based on the reference "AMINO ACID DIFFERENCE FORMULA TO HELP EXPLAIN PROTEIN EVOLUTION (1971), http://www.sciencemag.org/content/185/4154/862.long

You can find it in the original command "Grantham_score_calculator.py".

黎 于

This depends on your outgroup, if your allele in outgroup is 1/1, then 0/0 is the derived allele, so you still have to keep it. If you don't have a suitable outgroup, you can only define the ancestral alleles in terms of relatively high frequency alleles.

Tian Xia

Kunming Institute of Botany

张同学，请问您找出了于黎老师提供的这个python脚本的输入文件的格式了吗？

tian Xia

Southwest University

同学您好，我想问问大家在划分LOF的时候，除了于老师提到的几种类型，还包括了哪些类型呢？或者是否应该包含splice_region_variant 和stop_lost呢？

黎 于

Leu Pro

Ser Pro

Leu Ile

His Tyr

Arg Gly

Pro Leu

Pro Ala

Gly Arg

Ser Asn

Ile Thr

Glu Lys

Glu Gly

跃飞 汪

西北农林科技大学

missense_variants.vcf | grep -v '#' | awk -F"\t|\\\\|" '{printf ("%s\t%s\t%s\t%s\t%s\n", $18,$1,$2,$4,$5)}' | awk -F"\t" '{OFS = FS} { gsub(/p\./,"", $1); print }' | awk '{sub(/[0-9]+/," ",$1); print}'

可以通过以上代码将文件转化为输入文件

mx wu

中南林业科技大学研究生院

同学你好，我目前也有同样的疑问，请问你解决了吗，能否指教一下

黎 于

# Python

# Authorship: Guoliang Lin/Hu jingyang

# Date: 2022-12-16 11:11:11

import sys

def print_hi(name):

  print(f'Hi, {name}') 

Score_matrix={'Ser': {'Arg':110, 'Leu':145, 'Pro':74, 'Thr':58, 'Ala':99, 'Val':124, 'Gly':56, 'Ile':142, 'Phe':155, 'Try':144, 'Cys':112, 'His':89, 'Gln':68, 'Asn':46, 'Lys':121, 'Asp':65, 'Glu':80, 'Met':135, 'Trp':177},

'Arg': {'Arg':0, 'Leu':102, 'Pro':103, 'Thr':71, 'Ala':112, 'Val':96, 'Gly':125, 'Ile':97, 'Phe':97, 'Try':77, 'Cys':180, 'His':29, 'Gln':43, 'Asn':86, 'Lys':26, 'Asp':96, 'Glu':54, 'Met':91, 'Trp':101, 'Ser':0},

'Leu': {'Arg':0, 'Leu':0, 'Pro':98, 'Thr':92, 'Ala':96, 'Val':32, 'Gly':138, 'Ile':5, 'Phe':22, 'Try':36, 'Cys':198, 'His':99, 'Gln':113, 'Asn':153, 'Lys':107, 'Asp':172, 'Glu':138, 'Met':15, 'Trp':61, 'Ser':0},

'Pro': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':38, 'Ala':27, 'Val':68, 'Gly':42, 'Ile':95, 'Phe':114, 'Try':110, 'Cys':169, 'His':77, 'Gln':76, 'Asn':91, 'Lys':103, 'Asp':108, 'Glu':93, 'Met':87, 'Trp':147, 'Ser':0},

'Thr': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':58, 'Val':69, 'Gly':59, 'Ile':89, 'Phe':103, 'Try':92, 'Cys':149, 'His':47, 'Gln':42, 'Asn':65, 'Lys':78, 'Asp':85, 'Glu':65, 'Met':81, 'Trp':128, 'Ser':0},

'Ala': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':64, 'Gly':60, 'Ile':94, 'Phe':113, 'Try':112, 'Cys':195, 'His':86, 'Gln':91, 'Asn':111, 'Lys':106, 'Asp':126, 'Glu':107, 'Met':84, 'Trp':148, 'Ser':0},

'Val': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':109, 'Ile':29, 'Phe':50, 'Try':55, 'Cys':192, 'His':84, 'Gln':96, 'Asn':133, 'Lys':97, 'Asp':152, 'Glu':121, 'Met':21, 'Trp':88, 'Ser':0},

'Gly': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':135, 'Phe':153, 'Try':147, 'Cys':159, 'His':98, 'Gln':87, 'Asn':80, 'Lys':127, 'Asp':94, 'Glu':98, 'Met':127, 'Trp':184, 'Ser':0},

'Ile': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':21, 'Try':33, 'Cys':198, 'His':94, 'Gln':109, 'Asn':149, 'Lys':102, 'Asp':168, 'Glu':134, 'Met':10, 'Trp':61, 'Ser':0},

'Phe': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':22, 'Cys':205, 'His':100, 'Gln':116, 'Asn':158, 'Lys':102, 'Asp':177, 'Glu':140, 'Met':28, 'Trp':40, 'Ser':0},

'Try': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':194, 'His':83, 'Gln':99, 'Asn':143, 'Lys':85, 'Asp':160, 'Glu':122, 'Met':36, 'Trp':37, 'Ser':0},

'Cys': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':174, 'Gln':154, 'Asn':139, 'Lys':202, 'Asp':154, 'Glu':170, 'Met':196, 'Trp':215, 'Ser':0},

'His': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':24, 'Asn':68, 'Lys':32, 'Asp':81, 'Glu':40, 'Met':87, 'Trp':115, 'Ser':0},

'Gln': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':46, 'Lys':53, 'Asp':61, 'Glu':29, 'Met':101, 'Trp':130, 'Ser':0},

'Asn': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':0, 'Lys':94, 'Asp':23, 'Glu':42, 'Met':142, 'Trp':174, 'Ser':0},

'Lys': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':0, 'Lys':0, 'Asp':101, 'Glu':56, 'Met':95, 'Trp':110, 'Ser':0},

'Asp': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':0, 'Lys':0, 'Asp':0, 'Glu':45, 'Met':160, 'Trp':181, 'Ser':0},

'Glu': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':0, 'Lys':0, 'Asp':0, 'Glu':0, 'Met':126, 'Trp':152, 'Ser':0},

'Met': {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':0, 'Lys':0, 'Asp':0, 'Glu':0, 'Met':0, 'Trp':67, 'Ser':0},

'Trp':  {'Arg':0, 'Leu':0, 'Pro':0, 'Thr':0, 'Ala':0, 'Val':0, 'Gly':0, 'Ile':0, 'Phe':0, 'Try':0, 'Cys':0, 'His':0, 'Gln':0, 'Asn':0, 'Lys':0, 'Asp':0, 'Glu':0, 'Met':0, 'Trp':0 , 'Ser':0}}

if __name__ == '__main__':

  if len(sys.argv)<3:

    print("Error!")

    print("Usage:python get_score.py inputfile outputfile")

    sys.exit(-1)

  # print_hi('PyCharm')

  with open(sys.argv[1]) as infile:

    with open(sys.argv[2],'w') as outfile:

      for item in infile:

        item=item.strip()

        itemlist=item.split()

        if (itemlist[0] in Score_matrix) and (itemlist[1] in Score_matrix[itemlist[0]]):

          score=Score_matrix[itemlist[0]][itemlist[1]]

        else:

          score=0

        outfile.write(f"{itemlist[0]} {itemlist[1]} {score} ")

跃飞 汪

西北农林科技大学

老师，这个矩阵可能有问题，这个脚本写的0填充，但是我看原文章可能的意思是对称，类似下图
1 S R L P T A V G I F Y C H Q N K D E M W
S 0 110 145 74 58 99 124 56 142 155 144 112 89 68 46 121 65 80 135 177
R 110 0 102 103 71 112 96 125 97 97 77 180 29 43 86 26 96 54 91 101
L 145 102 0 98 92 96 32 138 5 22 36 198 99 113 153 107 172 138 15 61
P 74 103 98 0 38 27 68 42 95 114 110 169 77 76 91 103 108 93 87 147
T 58 71 92 38 0 58 69 59 89 103 92 149 47 42 65 78 85 65 81 128
A 99 112 96 27 58 0 64 60 94 113 112 195 86 91 111 106 126 107 84 148
V 124 96 32 68 69 64 0 109 29 50 55 192 84 96 133 97 152 121 21 88
G 56 125 138 42 59 60 109 0 135 153 147 159 98 87 80 127 94 98 127 184
I 142 97 5 95 89 94 29 135 0 21 33 198 94 109 149 102 168 134 10 61
F 155 97 22 114 103 113 50 153 21 0 22 205 100 116 158 102 177 140 28 40
Y 144 77 36 110 92 112 55 147 33 22 0 194 83 99 143 85 160 122 36 37
C 112 180 198 169 149 195 192 159 198 205 194 0 174 154 139 202 154 170 196 215
H 89 29 99 77 47 86 84 98 94 100 83 174 0 24 68 32 81 40 87 115
Q 68 43 113 76 42 91 96 87 109 116 99 154 24 0 46 53 61 29 101 130
N 46 86 153 91 65 111 133 80 149 158 143 139 68 46 0 94 23 42 142 174
K 121 26 107 103 78 106 97 127 102 102 85 202 32 53 94 0 101 56 95 110
D 65 96 172 108 85 126 152 94 168 177 160 154 81 61 23 101 0 45 160 181
E 80 54 138 93 65 107 121 98 134 140 122 170 40 29 42 56 45 0 126 152
M 135 91 15 87 81 84 21 127 10 28 36 196 87 101 142 95 160 126 0 67
W 177 101 61 147 128 148 88 184 61 40 37 215 115 130 174 110 181 152 67 0

黎 于

输入文件是SnpEff 注释的 vcf 文件中的missense variants位点，然后计算的方法是python脚本Grantham_score_calculator.py（https://github.com/ashutoshkpandey/Annotation/blob/master/Grantham_score_calculator.py）

Jie xiao

Huazhong agriculture university

请问这个Grantham_score_calculator.py具体如何使用呢？python Grantham_score_calculator.py missense.vcf 这个命令吗？谢谢

黎 于

这是一个python脚本。源代码是针对单个位点的计算。所以建议找熟悉python的人修改成批量执行，或者就是把vcf拆分成单个位点再去执行。