Blood-based multi-tissue gene expression inference with Bayesian ridge regression

2020 ◽  
Vol 36 (12) ◽  
pp. 3788-3794
Author(s):  
Wenjian Xu ◽  
Xuanshi Liu ◽  
Fei Leng ◽  
Wei Li

Abstract Motivation Gene expression profiling is widely used in basic and cancer research but still not feasible in many clinical applications because tissues, such as brain samples, are difficult and not ethnical to collect. Gene expression in uncollected tissues can be computationally inferred using genotype and expression quantitative trait loci. No methods can infer unmeasured gene expression of multiple tissues with single tissue gene expression profile as input. Results Here, we present a Bayesian ridge regression-based method (B-GEX) to infer gene expression profiles of multiple tissues from blood gene expression profile. For each gene in a tissue, a low-dimensional feature vector was extracted from whole blood gene expression profile by feature selection. We used GTEx RNAseq data of 16 tissues to train inference models to capture the cross-tissue expression correlations between each target gene in a tissue and its preselected feature genes in peripheral blood. We compared B-GEX with least square regression, LASSO regression and ridge regression. B-GEX outperforms the other three models in most tissues in terms of mean absolute error, Pearson correlation coefficient and root-mean-squared error. Moreover, B-GEX infers expression level of tissue-specific genes as well as those of non-tissue-specific genes in all tissues. Unlike previous methods, which require genomic features or gene expression profiles of multiple tissues, our model only requires whole blood expression profile as input. B-GEX helps gain insights into gene expressions of uncollected tissues from more accessible data of blood. Availability and implementation B-GEX is available at https://github.com/xuwenjian85/B-GEX. Supplementary information Supplementary data are available at Bioinformatics online.

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2285-2290 ◽  
Author(s):  
James Z. Huang ◽  
Warren G. Sanger ◽  
Timothy C. Greiner ◽  
Louis M. Staudt ◽  
Dennis D. Weisenburger ◽  
...  

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell–like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 911-911 ◽  
Author(s):  
Martin Neumann ◽  
Sandra Heesch ◽  
Stefan Schwartz ◽  
Nicola Gökbuget ◽  
Dieter Hoelzer ◽  
...  

Abstract Abstract 911 Introduction: Recently, a small subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was described, which is closely associated with the gene expression profile of early T-cell precursors (ETPs). This subtype, termed ETP-ALL, showed a highly unfavorable outcome compared to non-ETP(='typical')-ALL. Based on the results of Coustan-Smith et al. (Lancet Oncology, 2009), the Italian national study Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) and St-Jude Children's hospital modified their treatment in children with ETP-ALL to a more intensive regime including stem cell transplantation. ETP-ALL is characterized by a specific immunophenotype (CD1a-, CD8-, CD5weak with expression of stem cell or myeloid markers). Here we explored the existence of ETP-ALL in adults and further studied the molecular characteristics of this specific T-ALL subtype. Patients and methods: We examined the gene expression profiles of 86 adult T-ALL patients obtained from the Microarray Innovations in LEukemia (MILE) multicenter study (HG-U133 Plus 2.0, Affymetrix, Haferlach et al., JCO in press). In addition, bone marrow of 296 patients from the German Acute Lymphoblastic Leukemia Multicenter Study Group (GMALL) were analyzed by flow cytometry and expression levels of BAALC, IGFBP7, MN1, and WT1 were determined by real-time-PCR. Results: Using the published list of differentially expressed genes in ETPs (Coustan-Smith et al. 2009) we performed unsupervised clustering analyses of the 86 T-ALL samples. A cluster of 17 samples (19.8%) displayed an ETP-associated gene expression profile and were defined as ETP-ALL. Comparing the gene expression profiles of ETP-ALL and typical T-ALL, 2065 probe sets were differentially expressed in ETP-ALL (FDR 0.05). In addition to genes used for classification, we also identified genes known to be involved in the pathogenesis of T-ALL (e.g. PROM1, BCL2, LMO2, LYL1). In particular, stem cell associated genes such as, BAALC (2.52-fold, p=0.003), IGFBP7 (2.76-fold, p=0.002) or MN1 (3.41-fold, p<0.001) were upregulated in ETP-ALL, whereas HOX11 (45-fold, p=0.004), a marker for thymic T-ALL, was downregulated. An independent cohort of 297 patient samples from the GMALL study group was examined by flow cytometry and real-time PCR. 19 (6.4%) samples revealed the ETP-ALL immunophenotype. As expected, all patient samples were found in the group of early T-ALL, representing 23.5% of all early T-ALLs. There was a significant correlation between a lower leukocyte count at first diagnosis and the classification of ETP-ALL (p=0.001). Gene expression measured by real-time-PCR was performed for genes associated with poor outcome in T-ALL: BAALC (2.11-fold, p<0.001) and IGFBP7 (3.59-fold, p=0.003) were significantly upregulated in the group of ETP-ALL. Similarly, the genes MN1 (4.52-fold, p<0.001) and WT1 (2.76-fold, p=0.036), described as poor prognostic markers in cytogenetically normal AML, were also upregulated in ETP-ALL. Conclusion: In adult T-ALL, a subset of patients shares the gene expression profil and immunophenotype of ETP-ALL, which is in line with recent findings in pediatric patients. The gene expression profile of this subset is significantly correlated to stem cell associated markers predictive for inferior outcome in T-ALL. Interestingly, adverse factors in CN-AML are also aberrantly expressed in ETP-ALL suggesting a myeloid origin of ETPs and indicating a closer relationship between ETP-ALL and AML. The prognostic impact and the determination of the most appropiate set of markers needs to be further investigated. These results support the GMALL strategy to regard early T-ALL patients as high risk with assignment to stem cell transplantation. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership.


2004 ◽  
Vol 22 (6) ◽  
pp. 994-998 ◽  
Author(s):  
Ana Fernandez-Teijeiro ◽  
Rebecca A. Betensky ◽  
Lisa M. Sturla ◽  
John Y.H. Kim ◽  
Pablo Tamayo ◽  
...  

Purpose Stratification of risk in patients with medulloblastoma remains a challenge. As clinical parameters have been proven insufficient for accurately defining disease risk, molecular markers have become the focus of interest. Outcome predictions on the basis of microarray gene expression profiles have been the most accurate to date. We ask in a multivariate model whether clinical parameters enhance survival predictions of gene expression profiles. Patients and Methods In a cohort of 55 young patients (whose medulloblastoma samples have been analyzed previously for gene expression profile), associations between clinical and gene expression variables and survival were assessed using Cox proportional hazards models. Available clinical variables included age, stage (ie, the presence of disseminated disease at diagnosis), sex, histologic subtype, treatment, and status. Results Univariate analysis demonstrated expression profiles to be the only significant clinical prognostic factor (P = .03). In multivariate analysis, gene expression profiles predicted outcome independent of other criteria. Clinical criteria did not significantly contribute additional information for outcome predictions, although an exploratory analysis noted a trend for decreased survival of patients with metastases at diagnosis but favorable gene expression profile. Conclusion Gene expression profiling predicts medulloblastoma outcome independent of clinical variables. These results need to be validated in a larger prospective study.


PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96901 ◽  
Author(s):  
Yujing Jan Heng ◽  
Craig Edward Pennell ◽  
Hon Nian Chua ◽  
Jonathan Edward Perkins ◽  
Stephen James Lye

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84002 ◽  
Author(s):  
Samantha E. Tangen ◽  
Darwin Tsinajinnie ◽  
Martha Nuñez ◽  
Gabriel Q. Shaibi ◽  
Lawrence J. Mandarino ◽  
...  

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