Med edical Cen enter er for Infec ectious Disea eases es Ber erlin HIV-GRADE update Arevir Meeting 2018 Eva Heger Matthias Döring Martin Obermeier University of Cologne Max Planck Institute for Informatics MIB Berlin 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Updates in progress • Major changes are coming to HIV-GRADE • Change in structure of interpretation • Update of interface • Integration of APOBEC mutation data • NGS data analysis 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Switching from 4 categories to 3 categories • HIV-GRADE interpretation is currently using four different categories • Susceptible • Limited susceptibility • Intermediate Resistance • Resistance • Category Limited susceptibility will be removed as overinterpretation of this category often has occurred ,leaving categories • Susceptible • Intermediate Resistance • Resistance • Mark-up of specific mutations 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Example DTG Resistent Intermediate Resistance Limited Susceptibility • Q148HKR + 2 out of (G140ACS, • Q148HKR + 1 out of (G140ACS, L74IM, • A49G • Q148HKR • T66I • N155H L74IM, E138AKT) E138AKT) • L74I • 148RH + 140S • N155H + 1 out of ( E92Q, T97A, • S230GR • E92Q • V260I Y143R, L74IM, E138AKT) • T97A • R263K • G140ACS • G118R • Y143R OLD • E138AKT • S147G Resistent Intermediate Resistance Marked up mutations • Q148HKR + 1 aus • R263K • L74I • S147G (G140ACS, L74IM, E138AKT, • Q148HKR • E138AT • S230G N155H) • G140ACS • V260I • T66I • 157Q • N155H + E92Q • N155H • T97A • G118R • Y143R • S230R NEW • E138K • E92Q 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Example DTG Resistent Intermediate Resistance Marked up mutations • Q148HKR + 1 aus • R263K • L74I • S147G (G140ACS, L74IM, • Q148HKR • E138AT • S230G E138AKT, N155H) • G140ACS • V260I • T66I • 157Q • N155H + E92Q • N155H • T97A DTG qd • G118R • Y143R • S230R • E138K • E92Q Resistent Intermediate Resistance Marked up mutations • Q148HKR + 2 aus • Q148HKR + 1 aus • R263K • G118R (G140ACS, L74IM, (G140ACS, L74IM, E138AKT, • Q148HKR • S230R DTG bid E138AKT, N155H) N155H) • G140ACS • E138K • N155H + E92Q • N155H 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Update of interface 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Integration of APOBEC mutations TARGET TARGET-POS REF-AA APO-AA APO-CODON SUBTYPES 43_02G;10_CD;04_cpx;D;G;02_AG;06_cpx;21 RT 178 M I ATA _A2D;34_01B;15_01B;38_BF1;33_01B;32_06 A1;01_AE RT 179 E K AAA 38_BF1 RT 182 R Q CAA 16_A2D 16_A2D;11_cpx;47_BF;20_BG;37_cpx;36_cpx; 18_cpx;01_AE;46_BF;12_BF;10_CD;31_BC;25 _cpx;09_cpx;06_cpx;22_01A1;19_cpx;21_A2D ;A1;35_AD;07_BC;A2;15_01B;42_BF;40_BF;2 9_BF;02_AG;32_06A1;13_cpx;C;B;D;G;F1;34_ 01B;26_AU;38_BF1;33_01B;27_cpx;F2;08_BC RT 184 M I ATA ;04_cpx;28_BF;44_BF;43_02G;17_BF;03_AB; 23_BG;14_BG;45_cpx;24_BG;49_cpx;05_DF 16_A2D;11_cpx;47_BF;20_BG;37_cpx;36_cpx; 18_cpx;01_AE;46_BF;12_BF;10_CD;31_BC;25 _cpx;09_cpx;06_cpx;22_01A1;19_cpx;21_A2D ;A1;35_AD;07_BC;A2;15_01B;42_BF;40_BF;2 9_BF;02_AG;32_06A1;13_cpx;C;B;D;G;F1;34_ 01B;26_AU;38_BF1;33_01B;27_cpx;F2;08_BC ;04_cpx;28_BF;44_BF;43_02G;17_BF;03_AB; RT 185 D N AAT 23_BG;14_BG;45_cpx;24_BG;49_cpx;39_BF;0 5_DF 16_A2D;11_cpx;47_BF;20_BG;17_BF;36_cpx; 21_A2D;29_BF;46_BF;12_BF;10_CD;31_BC;2 5_cpx;09_cpx;06_cpx;19_cpx;18_cpx;07_BC;4 2_BF;40_BF;02_AG;32_06A1;B;D;G;43_02G;3 4_01B;38_BF1;F1;F2;04_cpx;28_BF;03_AB;23 RT 186 D N AAT _BG;14_BG;45_cpx;24_BG;49_cpx;39_BF;05_ DF 13_cpx;27_cpx;C;08_BC;26_AU;44_BF;11_cp x;25_cpx;45_cpx;22_01A1;17_BF;A1;35_AD;3 RT 186 D N AAC 7_cpx;A2;46_BF;15_01B;38_BF1;33_01B;01_ AE 13_cpx;F1;F2;46_BF;04_cpx;49_cpx;11_cpx;0 RT 190 G R AGG 9_cpx;06_cpx;22_01A1;18_cpx;45_cpx;40_BF; 05_DF 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
NGS • Participation in the standardization approach of • Direct interpretation of this data format in the HIV-GRADE tool • Close cooperation with 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Acknowledgements 5/2018 Med edical C Cen enter er for or Inf nfectious us Disease ses Berlin lin
Recommend
More recommend
