A Dirichlet-Multinomial Mixture Model For Clustering Heterogeneous Epigenomics Data

Epigenetic information sheds light on essential biological mechanisms including the regulation of gene expression. Among the major epigenetic mechanisms are histone tail modifications which can be utilized to identify cis-regulatory elements such as promoters and enhancers. Nucleosome positions and open chromatin regions are other key elements of the epigenomic landscape. Thanks to the advances in high-throughput sequencing technologies, comprehensive genome-wide analyses of epigenetic signatures are possible at present. Despite the growing number of epigenetic datasets, the tools to discover novel patterns and combinatorial presence of epigenetic elements are still needed. In this thesis, we introduce a model-based clustering approach that uncovers epigenetic patterns by integrating multiple data tracks in a multi-view fashion where different views correspond to different epigenetic signals extracted from the same genomic location. Moreover, to address the inaccuracy of the positions of anchor points, such as TF ChIP-seq peak summits or TSS, a profile shifting feature is implemented. Finally, owing to the hyperprior regularization, our approach can also account for the correlation between the number of reads mapped to consecutive base pair positions. We demonstrate that the genome-wide clustering of promoter and enhancer regions in human genome reveals distinct patterns in various histone modification and transcription factor ChIP-seq profiles. Furthermore, TFBS enrichment in different classes of enhancers and promoters that are identified by our method is investigated which shows that some transcription factors are significantly enriched in a subset of enhancer and promoter clusters

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study

Aim: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). Patients and methods: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. Results: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. Conclusion: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations