Molecular classificaiton of ALL with whole transcriptome sequencing analysis in a Taiwan cohort
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE207057 | GEO | 2022/08/03
REPOSITORIES: GEO
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Project description:Background: Although genetic or epigenetic alterations have shown to affect the three-dimensional organization of genomes, the utility of chromatin conformation in the classification of human disease has never been addressed. Results: Here, we explore whether chromatin conformation can be used to classify human leukemia. We map the conformation of the HOXA gene cluster in a panel of cell lines with 5C chromosome conformation capture technology, and use the data to train and test a support vector machine classifier named 3D-SP. We show that 3D-SP is able to accurately distinguish leukemias expressing MLL-fusion proteins from those expressing only wild-type MLL, and that it can also classify leukemia subtypes according to MLL fusion partner, based solely on 5C data. Conclusions: Our study provides the first proof-of-principle demonstration that chromatin conformation contains the information value necessary for classification of leukemia subtypes. Examination of CTCF and RAD21 binding sites in THP-1 cell.
2014-02-27 | E-GEOD-55407 | biostudies-arrayexpress
Project description:Background: Although genetic or epigenetic alterations have shown to affect the three-dimensional organization of genomes, the utility of chromatin conformation in the classification of human disease has never been addressed. Results: Here, we explore whether chromatin conformation can be used to classify human leukemia. We map the conformation of the HOXA gene cluster in a panel of cell lines with 5C chromosome conformation capture technology, and use the data to train and test a support vector machine classifier named 3D-SP. We show that 3D-SP is able to accurately distinguish leukemias expressing MLL-fusion proteins from those expressing only wild-type MLL, and that it can also classify leukemia subtypes according to MLL fusion partner, based solely on 5C data. Conclusions: Our study provides the first proof-of-principle demonstration that chromatin conformation contains the information value necessary for classification of leukemia subtypes. Analysis of 38 samples using 5C technology. All data normalized using a 'master' BAC consisting of 5C data from 6 samples.
2014-02-27 | E-GEOD-55406 | biostudies-arrayexpress
Project description:Background: Although genetic or epigenetic alterations have shown to affect the three-dimensional organization of genomes, the utility of chromatin conformation in the classification of human disease has never been addressed. Results: Here, we explore whether chromatin conformation can be used to classify human leukemia. We map the conformation of the HOXA gene cluster in a panel of cell lines with 5C chromosome conformation capture technology, and use the data to train and test a support vector machine classifier named 3D-SP. We show that 3D-SP is able to accurately distinguish leukemias expressing MLL-fusion proteins from those expressing only wild-type MLL, and that it can also classify leukemia subtypes according to MLL fusion partner, based solely on 5C data. Conclusions: Our study provides the first proof-of-principle demonstration that chromatin conformation contains the information value necessary for classification of leukemia subtypes.
2014-02-27 | GSE55407 | GEO
Project description:Background: Although genetic or epigenetic alterations have shown to affect the three-dimensional organization of genomes, the utility of chromatin conformation in the classification of human disease has never been addressed. Results: Here, we explore whether chromatin conformation can be used to classify human leukemia. We map the conformation of the HOXA gene cluster in a panel of cell lines with 5C chromosome conformation capture technology, and use the data to train and test a support vector machine classifier named 3D-SP. We show that 3D-SP is able to accurately distinguish leukemias expressing MLL-fusion proteins from those expressing only wild-type MLL, and that it can also classify leukemia subtypes according to MLL fusion partner, based solely on 5C data. Conclusions: Our study provides the first proof-of-principle demonstration that chromatin conformation contains the information value necessary for classification of leukemia subtypes.
2014-02-27 | GSE55406 | GEO
Project description:Abstract Mutations in the gene encoding nucleophosmin (NPM1) carry prognostic value for patients with acute myeloid leukemia (AML). Various techniques are currently being used to detect these mutations in routine molecular diagnostics. Incorporation of accurate NPM1 mutation detection on a gene expression platform would enable simultaneous detection with various other expression biomarkers. Here we present an array based mutation detection using custom probes for NPM1 WT mRNA and NPM1 type A, B, and D mutant mRNA. This method was 100% accurate on a training cohort of 505 newly diagnosed unselected AML cases. Validation on an independent cohort of 143 normal karyotype AML cases revealed no false negative results, and one false positive (sensitivity 100.0%, and specificity 98.7%). Based on this, we conclude that this method provides a reliable method for NPM1 mutation detection. The method can be applied to other genes/mutations as long as the mutant alleles are sufficiently high expressed. Validation cohort of 143 AML cases analyzed using the AMLprofiler
2013-01-01 | E-GEOD-42200 | biostudies-arrayexpress
Project description:Abstract Mutations in the gene encoding nucleophosmin (NPM1) carry prognostic value for patients with acute myeloid leukemia (AML). Various techniques are currently being used to detect these mutations in routine molecular diagnostics. Incorporation of accurate NPM1 mutation detection on a gene expression platform would enable simultaneous detection with various other expression biomarkers. Here we present an array based mutation detection using custom probes for NPM1 WT mRNA and NPM1 type A, B, and D mutant mRNA. This method was 100% accurate on a training cohort of 505 newly diagnosed unselected AML cases. Validation on an independent cohort of 143 normal karyotype AML cases revealed no false negative results, and one false positive (sensitivity 100.0%, and specificity 98.7%). Based on this, we conclude that this method provides a reliable method for NPM1 mutation detection. The method can be applied to other genes/mutations as long as the mutant alleles are sufficiently high expressed. Training cohort of 505 AML cases analyzed using the AMLprofiler
2013-01-01 | E-GEOD-42194 | biostudies-arrayexpress
Project description:Background: Since 2016, a project for molecular diagnosis of childhood medulloblastoma (MB) was initiated in Taiwan. We aimed to integrate molecular classification, molecular and clinical risk factors, somatic mutations, and phenotypic traits for up to date adaptive care. Method: 18 MBs in children with frozen tumor tissue were assembled. Clinical data were retrieved. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping and molecular-clinical correlation were performed. Subgroup-based risk stratification included an adjusted Heidelberg risk stratification scheme were defined and evaluated. We selected 51 genes for somatic variant calling using RNA-Seq. Relevant phenotypic traits were defined for the linkage of genetic predisposition. Results: Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The overall survivals of the adjusted Heidelberg scheme matched with the definition of each risk subgroups. Somatic mutations in DNA damage response were detected. Conclusion: The findings of this study provide valuable information for adaptive risk stratified treatment and personalized care of childhood MBs in our cohort series and in Taiwan.
2022-05-18 | GSE158413 | GEO
Project description:Background: Since 2016, a project for molecular diagnosis of childhood medulloblastoma (MB) was initiated in Taiwan. We aimed to integrate molecular classification, molecular and clinical risk factors, somatic mutations, and phenotypic traits for up to date adaptive care. Method: Fifty-two MBs in children with frozen tumor tissue were assembled. Clinical data were retrieved. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping and molecular-clinical correlation were performed. Subgroup-based risk stratification included an adjusted Heidelberg risk stratification scheme were defined and evaluated. We selected 51 genes for somatic variant calling using RNA-Seq. Relevant phenotypic traits were defined for the linkage of genetic predisposition. Results: Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The overall survivals of the adjusted Heidelberg scheme matched with the definition of each risk subgroups. Somatic mutations in DNA damage response were detected. Five patients with SHH MB presented potential genetic predisposition and three patients had related germline mutations. Conclusion: The findings of this study provide valuable information for adaptive risk stratified treatment and personalized care of childhood MBs in our cohort series and in Taiwan.
2022-05-18 | GSE143940 | GEO
Project description:Sequential NGS for PhALL
| PRJEB48507 | ENA
Project description:Abstract Mutations in the gene encoding nucleophosmin (NPM1) carry prognostic value for patients with acute myeloid leukemia (AML). Various techniques are currently being used to detect these mutations in routine molecular diagnostics. Incorporation of accurate NPM1 mutation detection on a gene expression platform would enable simultaneous detection with various other expression biomarkers. Here we present an array based mutation detection using custom probes for NPM1 WT mRNA and NPM1 type A, B, and D mutant mRNA. This method was 100% accurate on a training cohort of 505 newly diagnosed unselected AML cases. Validation on an independent cohort of 143 normal karyotype AML cases revealed no false negative results, and one false positive (sensitivity 100.0%, and specificity 98.7%). Based on this, we conclude that this method provides a reliable method for NPM1 mutation detection. The method can be applied to other genes/mutations as long as the mutant alleles are sufficiently high expressed.
2013-01-01 | GSE42200 | GEO