Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dependent generalized Dirichlet process priors for the analysis of acute lymphoblastic leukemia.

ABSTRACT: We propose a novel Bayesian nonparametric process prior for modeling a collection of random discrete distributions. This process is defined by including a suitable Beta regression framework within a generalized Dirichlet process to induce dependence among the discrete random distributions. This strategy allows for covariate dependent clustering of the observations. Some advantages of the proposed approach include wide applicability, ease of interpretation, and availability of efficient MCMC algorithms. The motivation for this work is the study of the impact of asparginage metabolism on lipid levels in a group of pediatric patients treated for acute lymphoblastic leukemia.

SUBMITTER: Barcella W

PROVIDER: S-EPMC6959469 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Dependent generalized Dirichlet process priors for the analysis of acute lymphoblastic leukemia.

Barcella William W De Iorio Maria M Favaro Stefano S Rosner Gary L GL

Biostatistics (Oxford, England) 20180701 3

We propose a novel Bayesian nonparametric process prior for modeling a collection of random discrete distributions. This process is defined by including a suitable Beta regression framework within a generalized Dirichlet process to induce dependence among the discrete random distributions. This strategy allows for covariate dependent clustering of the observations. Some advantages of the proposed approach include wide applicability, ease of interpretation, and availability of efficient MCMC algo ...[more]

PMID: 28968716

Similar Datasets

Mutation analysis of isocitrate dehydrogenase in acute lymphoblastic leukemia.

Project description:Mutations at arginine 132 of isocitrate dehydrogenase 1/2 (IDH1/2) have recently been demonstrated to be recurrent gene alterations in acute myeloid leukemia (AML). Subsequently, this mutation was also found in a variety of other hematologic malignancies, including myelodysplastic syndromes, myeloproliferative diseases, and non-Hodgkin lymphoma. Only a few cases were so far identified in acute lymphoblastic leukemia (ALL). To study the IDH status in ALL patients, we analyzed 54 adult and 34 pediatric ALL samples' IDH1/2 gene.Three adult cases and no pediatric case with an isocitrate dehydrogenase 1 (IDH1) mutation were identified. No isocitrate dehydrogenase 2 (IDH2) mutation was identified in the total of 88 samples. The frequency of the IDH1 mutation in adult ALL was 5.5%. Among the three IDH1-mutated patients, two had normal karyotype and expressed the myeloid lineage markers. All three patients with an IDH1 mutation relapsed or died within 6 months.The results suggested that the IDH1 R132 mutation might be a recurrent gene alteration in ALL; patients carrying the mutation have a trend to aberrantly express myeloid antigen and the mutation may imply a dismal outcome.

| S-EPMC3422558 | biostudies-other

Incorporating Domain Knowledge into Topic Modeling via Dirichlet Forest Priors.

Project description:Users of topic modeling methods often have knowledge about the composition of words that should have high or low probability in various topics. We incorporate such domain knowledge using a novel Dirichlet Forest prior in a Latent Dirichlet Allocation framework. The prior is a mixture of Dirichlet tree distributions with special structures. We present its construction, and inference via collapsed Gibbs sampling. Experiments on synthetic and real datasets demonstrate our model's ability to follow and generalize beyond user-specified domain knowledge.

| S-EPMC2943854 | biostudies-literature

Monoclonal antibodies in acute lymphoblastic leukemia.

Project description:With modern intensive combination polychemotherapy, the complete response (CR) rate in adults with acute lymphoblastic leukemia (ALL) is 80% to 90%, and the cure rate is 40% to 50%. Hence, there is a need to develop effective salvage therapies and combine novel agents with standard effective chemotherapy. ALL leukemic cells express several surface antigens amenable to target therapies, including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic surface antigens selectively and minimize off-target toxicity. When added to frontline chemotherapy, rituximab, an antibody directed against CD20, increases cure rates of adults with Burkitt leukemia from 40% to 80% and those with pre-B ALL from 35% to 50%. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6 to 7 months when given to patients with refractory-relapsed ALL. Blinatumomab, a biallelic T cell engaging the CD3-CD19 monoclonal antibody, also resulted in overall response rates of 40% to 50% and a median survival of 6.5 months in a similar refractory-relapsed population. Other promising monoclonal antibodies targeting CD20 (ofatumumab and obinutuzumab) or CD19 or CD20 and bound to different cytotoxins or immunotoxins are under development. Combined modalities of chemotherapy and the novel monoclonal antibodies are under investigation.

| S-EPMC4548495 | biostudies-other

Genetic abnormalities associated with acute lymphoblastic leukemia.

Project description:Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next-generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome-like B-lineage ALL is one of the new high-risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole-genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm-related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies.

| S-EPMC4968601 | biostudies-other

Population analysis of pharmacogenetic polymorphisms related to acute lymphoblastic leukemia drug treatment.

Project description:This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL), and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.

| S-EPMC3826589 | biostudies-other

Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia.

Project description:PFKP (phosphofructokinase, platelet), the major isoform of PFK1 expressed in T cell acute lymphoblastic leukemia (T-ALL), is predominantly expressed in the cytoplasm to carry out its glycolytic function. Our study showed that PFKP is a nucleocytoplasmic shuttling protein with functional nuclear export and nuclear localization sequences (NLSs). Cyclin D3/CDK6 facilitated PFKP nuclear translocation by dimerization and by exposing the NLS of PFKP to induce the interaction between PFKP and importin 9. Nuclear PFKP stimulated the expression of C-X-C chemokine receptor type 4 (CXCR4), a chemokine receptor regulating leukemia homing/infiltration, to promote T-ALL cell invasion, which depended on the activity of c-Myc. In vivo experiments showed that nuclear PFKP promoted leukemia homing/infiltration into the bone marrow, spleen, and liver, which could be blocked with CXCR4 antagonists. Immunohistochemical staining of tissues from a clinically well-annotated cohort of T cell lymphoma/leukemia patients showed nuclear PFKP localization in invasive cancers, but not in nonmalignant T lymph node or reactive hyperplasia. The presence of nuclear PFKP in these specimens correlated with poor survival in patients with T cell malignancy, suggesting the potential utility of nuclear PFKP as a diagnostic marker.

| S-EPMC8363288 | biostudies-literature

Zero-inflated generalized Dirichlet multinomial regression model for microbiome compositional data analysis.

Project description:There is heightened interest in using high-throughput sequencing technologies to quantify abundances of microbial taxa and linking the abundance to human diseases and traits. Proper modeling of multivariate taxon counts is essential to the power of detecting this association. Existing models are limited in handling excessive zero observations in taxon counts and in flexibly accommodating complex correlation structures and dispersion patterns among taxa. In this article, we develop a new probability distribution, zero-inflated generalized Dirichlet multinomial (ZIGDM), that overcomes these limitations in modeling multivariate taxon counts. Based on this distribution, we propose a ZIGDM regression model to link microbial abundances to covariates (e.g. disease status) and develop a fast expectation-maximization algorithm to efficiently estimate parameters in the model. The derived tests enable us to reveal rich patterns of variation in microbial compositions including differential mean and dispersion. The advantages of the proposed methods are demonstrated through simulation studies and an analysis of a gut microbiome dataset.

| S-EPMC7410344 | biostudies-literature

Ph-like acute lymphoblastic leukemia.

Project description:Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a newly identified high-risk (HR) B-lineage ALL subtype, accounting for ?15% of children with National Cancer Institute-defined HR B-ALL. It occurs more frequently in adolescents and adults, having been reported in as much as 27% of young adults with ALL between 21 and 39 years of age. It exhibits adverse clinical features, confers a poor prognosis, and harbors a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, making it amenable to treatment with tyrosine kinase inhibitor (TKI) therapy. Multiple groups are currently conducting clinical trials to prospectively screen patients with Ph-like ALL and incorporate the relevant TKI for those harboring ABL-class gene rearrangements or those with JAK-STAT pathway alterations. The success of combinatorial treatment of TKI with chemotherapy in the setting of Ph-positive ALL suggests that this approach may similarly improve outcomes for patients with Ph-like ALL. Hence, Ph-like ALL illustrates the modern treatment paradigm of precision medicine and presents unique opportunities for harnessing international collaborations to further improve outcomes for patients with ALL.

| S-EPMC6142516 | biostudies-literature

T-cell acute lymphoblastic leukemia.

Project description:T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included. Recent insights into T-ALL biology, using modern genomic techniques, have identified a number of recurrent lesions that can be grouped into several targetable pathways, including Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK. With contemporary chemotherapy, outcomes for de novo T-ALL have steadily improved and now approach those observed in B-ALL, with approximately 85% 5-year event-free survival. Unfortunately, salvage has remained poor, with less than 25% event-free and overall survival rates for relapsed disease. Thus, current efforts are focused on preventing relapse by augmenting therapy for high-risk patients, sparing toxicity in favorable subsets and developing new approaches for the treatment of recurrent disease.

| S-EPMC6142501 | biostudies-literature

Pharmacogenetics in acute lymphoblastic leukemia.

Project description:Progress in the treatment of acute lymphoblastic leukemia (ALL) in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric ALL. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm.

| S-EPMC2665795 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data