MALBAC Technology and Its Application in Non-invasive Chromosome Screening (NICS)
The Power of One Adapted from Internet
Single Cell Genomic Studies Ultra Low Sample Input Advances and applications of single-cell sequencing technologies. Wang Y et al. Mol Cell. 2015
Single Cell Genomic Studies Downstream Analysis Single cell pg level DNA ng to µg level DNA MALBAC TM single cell whole genome amplification (WGA) technology (Multiple Annealing and Looping Based Amplification Cycles)
Coverage MALBAC TM Single Cell WGA Technology Genome-Wide Detection of Single Nucleotide and Copy Number Variations of a Single Human Cell, Science, 2012
MALBAC TM Single Cell WGA Technology - Sensitivity Single cell Single chromosome Limited amount of tissue samples Genomic DNA
Coverage MALBAC TM Single Cell WGA Technology - Genome Coverage MALBAC MDA Genome-Wide Detection of Single Nucleotide and Copy Number Variations of a Single Human Cell, Science, 2012
MALBAC Uniformity TM Single Cell WGA Technology - Uniformity Single-Cell Whole-Genome Amplification and Sequencing: Methodology and Applications, Annu. Rev. Genomics Hum. Genet. 2015
MALBAC TM Single Cell WGA Technology Allele Drop Rate (ADO) A True Genotype B ADO Single-Cell Whole-Genome Amplification and Sequencing: Methodology and Applications, Annu. Rev. Genomics Hum. Genet. 2015
Features of MALBAC TM Single Cell WGA Technology High Genome Coverage High Uniformity High Sensitivity Low Allele Drop Out Rate
MALBAC TM Single Cell WGA Technology Single cell pg level DNA MALBAC TM Amplification Next Generation Sequencing (NGS) Microarray qpcr Molecular Cloning.
The Application of MALBAC TM Technology 2012 2012 2013 2013 2014 2015 2015 2016 2016 Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell. Science, 2012, 338, 1622. Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing. Science, 2012, 338(6114, 1627-1630) Genome Analyses of Single Human Oocytes. Cell, 2013, 155: 1492-1506 Reproducible Copy Number Variation Patterns Among Single Circulating Tumor Cells of Lung Cancer Patients. PNAS, 2013, 110(52): 21083-21088 Validation of multiple annealing and looping-based amplification cycle sequencing for 24-chromosome aneuploidy screening of cleavage-stage embryos. Fertility and Sterility, 2014, 102: 1685-1691 Single-Cell Whole-Genome Amplification and Sequencing: Methodology and Applications. Annu. Rev. Genomics Hum. Genet., 2015, 16: 16.1-16.24 Live Births after Simultaneous Avoidance of Monogenic Diseases and Chromosome Abnormality by Next-Generation Sequencing with Linkage Analyses. PNAS, 2015, 112(52):15964-9 A New Next-generation Sequencing-based Assay for Concurrent Preimplantation Genetic Diagnosis of Charcot-Marie- Tooth Disease Type A1 and Aneuploidy Screening. JGG, 2016, Available online 21 January 2016 Validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of blastocysts. Fertility and Sterility, 2016
Application of MALBAC TM Technology Single Cell Genomic Studies Lu S et al, 2012, Science, 338: 1627-1630 Hou Y et a., Cell. 2013 Dec 19;155(7):1492-506.
Application of MALBAC TM Technology in Cancer Genomic Studies Profiling of CTCs Xi. Ni, et al., PNAS.2013.12(52) 21083 21088.
Application of MALBAC TM Technology in Reproductive Genetic Testing Huang J et al. Fertil & steril, 2014; 102: 1685-1691 Huang J et a.l, Fertil Steril. 2016 Jun;105(6):1532-6.
Results of MALBAC TM -PGS (Preimplantation Genetic Screening) 47,XN,+4 Multiple Chromosomal Aneuploidy 46,XN 46,XN,+6q(q24.1 qter) 46,XN,-5 (mos*)
Conventional Preimplantation Genetic Screening Oocyte In Vitro Fertilization Embryo Culture Embryo Biopsy Sample Prep CGH Array Fish NGS Result Reporting
Non-invasive Chromosomal Screening (NICS) Technology Result Reporting Blastocyst
Features of NICS Non-invasive Embryos remain intact and only culture medium will be collected Convenience No need for embryo biopsy; Less strict requirements on equipment and techniques No sample loss Effectively address the sample loss issue during conventional PGS High sensitivity Can detect pg level genetic materials Flexible Compatible with both Illumina and Ion Torrent NGS platforms
Validation of NICS Culture Medium NICS Assay 42 Blastocyst Stage Embryos PGS Result Whole Embryo Conventional PGS Key Performance Parameters Specificity 84.0% Sensitivity 88.2% Positive predictive value (PPV) 78.9% Negative predictive value (NPV) 91.3% Xu J, et al. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. PNAS, 2016.
Validation of NICS
Clinical Application of NICS IVF Cycles Wife Husband 3 Premature ovarian failure No. of Blastocyst Embryos No. of Transferrable Embryos Clinical Outcome t(14;15)(q22;q24) 3 1 Healthy boy was born at 38 +4 wk
Clinical Application of NICS IVF Cycles Wife Husband 3 Premature ovarian failure No. of Blastocyst Embryos No. of Transferrable Embryos Clinical Outcome t(14;15)(q22;q24) 3 1 Healthy boy was born at 38 +4 wk Embryo 1 Medium 1 Embryo 2 Medium 2 Medium 3
Non-invasive Chromosomal Screening (NICS)
Future of MALBAC TM Technology Faster Simpler Compatible
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