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[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Soft Power of Nonconsensus Protein-DNA Binding.

Soft power of non-consensus protein-DNA binding

We have developed a software suite for the biophysical analysis of high-throughput sequencing experiments, and applied it to the interplay between nucleosome positioning, DNA methylation and transcription factor binding during ES cell differentiation. DNA cytosine methylation (5mC) and hydroxymethylation (5hmC) are among the most important epigenetic marks. The interplay of 5mC/5hmC marks, the arrangement of nucleosomes and transcription factors (TFs) links DNA methylation with cellular gene expression programs but the underlying mechanisms are poorly understood. Here, we analyzed nucleosome positioning, DNA methylation and TF binding in conjunction with additional dinucleosome occupancy maps. Our study provides a novel quantitative description for the relations between DNA methylation/demethylation, TF binding and nucleosome occupancy changes.

https://journal.embnet.org/index.php/embnetjournal/article/download/627/858

Developing a software suite to analyze the interplay between nucleosome arrangement, DNA methylation and transcription factor binding

Nucleosome positioning is an important process required for proper genome packing and its accessibility to execute the genetic program in a cell-specific, timely manner. In the recent years hundreds of papers have been devoted to the bioinformatics, physics and biology of nucleosome positioning. The purpose of this review is to cover a practical aspect of this field, namely to provide a guide to the multitude of nucleosome positioning resources available online. These include almost 300 experimental datasets of genome-wide nucleosome occupancy profiles determined in different cell types and more than 40 computational tools for the analysis of experimental nucleosome positioning data and prediction of intrinsic nucleosome formation probabilities from the DNA sequence. A manually curated, up to date list of these resources will be maintained at this http URL.

Nucleosome positioning: resources and tools online

Nucleosome positioning is involved in many gene regulatory processes happening in the cell and it may change as cells differentiate or respond to the changing microenvironment in a healthy or diseased organism. One important implication of nucleosome positioning in clinical epigenetics is its use in the "nucleosomics" analysis of cell-free DNA (cfDNA) for the purpose of patient diagnostics in liquid biopsies. The rationale for this is that the apoptotic nucleases that digest chromatin of the dying cells mostly cut DNA between nucleosomes. Thus, the short pieces of DNA in body fluids reflect the positions of nucleosomes in the cells of origin. Here we report a systematic nucleosomics database - NucPosDB, curating published nucleosome positioning datasets in vivo as well as datasets of sequenced cell-free DNA (cfDNA) that reflect nucleosome positioning in situ in the cells of origin. Users can select subsets of the database by a number of criteria and then obtain raw or processed data. NucPosDB also reports the originally determined regions with stable nucleosome occupancy across several individuals with a given condition. An additional section provides a catalogue of computational tools for the analysis of nucleosome positioning or cfDNA experiments and theoretical algorithms for the prediction of nucleosome positioning from DNA sequence. We provide an overview of the field, describe the structure of the database in this context and demonstrate data variability using examples of different medical conditions. NucPosDB is useful both for analysis of fundamental gene regulation processes and training computational models for patient diagnostics based on cfDNA. The database currently curates [~]400 publications on nucleosome positioning in cell lines and in situ as well as cfDNA from >10,000 patients and healthy volunteers. For open-access cfDNA datasets as well as key MNase-seq datasets in human cells, NucPosDB allows downloading processed mapped data in addition to the stable-nucleosome regions. NucPosDB is available at https://generegulation.org/nucposdb/.

https://biorxiv.org/content/10.1101/2021.11.24.469884v1.full.pdf

Vladimir B. Teif

Papers

Soft Power of Nonconsensus Protein-DNA Binding.

Soft power of non-consensus protein-DNA binding

Developing a software suite to analyze the interplay between nucleosome arrangement, DNA methylation and transcription factor binding

Nucleosome positioning: resources and tools online

NucPosDB: a database of nucleosome positioning in vivo and nucleosomics of cell-free DNA