The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

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An integrated encyclopedia of DNA elements in the human genome

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Tissue-based map of the human proteome

An integrated encyclopedia of DNA elements in the human genome.

The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.

NCBI GEO: archive for functional genomics data sets—update

A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

The single-molecule multiplex chromatin interaction data generated by emerging non-ligation-based 3D genome mapping technologies provide novel insights into high dimensional chromatin organization, yet introduce new computational challenges. We developed MIA-Sig (https://github.com/TheJacksonLaboratory/mia-sig.git), an algorithmic framework to de-noise the data, assess the statistical significance of chromatin complexes, and identify topological domains and inter-domain contacts. On chromatin immunoprecipitation (ChIP)-enriched data, MIA-Sig can clearly distinguish the protein-associated interactions from the non-specific topological domains.

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Multiplex chromatin interaction analysis by signal processing and statistical algorithms

In the past decade, genome-wide characterization of the three-dimensional chromatin structure in plants using high-throughput methods has greatly advanced our knowledge in plant genome architecture (Liu and Weigel, 2015; Ouyang et al., 2020). However, due to the limitation of Illumina short-read sequencing, the genome-wide contact map obtained by Hi-C/ChIA-PET is pairwise, and the multi-way interaction can only be inferred from the two-way data. To directly capture multi-way interaction in Arabidopsis, we applied a long-read-based method called Pore-C that directly sequences the DNA fragments joined by proximity-based ligation (Ulahannan et al., 2019).

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Pore-C Simultaneously Captures Genome-wide Multi-way Chromatin Interaction and Associated DNA Methylation Status in Arabidopsis

The present invention provides a method for next generation chromatin interaction assays based on the single molecule protein-detection and DNA-sequencing platform at the single molecule and single nucleus single molecule levels. The present invention has the advantages of single molecule resolution in single nuclei and the elimination of proximity ligation and PCR amplification steps. The present invention provides revolutionary biological insights in the organization of the 3D genome and its modulation.

Single nucleus and single molecule chromatin interaction assays

The emerging ligation-free three-dimensional (3D) genome mapping technologies can identify multiplex chromatin interactions with single-molecule precision. These technologies offer new insight into high-dimensional chromatin organization and gene regulation, but also introduce new challenges in data visualization and analysis. To overcome these challenges, we developed MCIBox, a toolkit for Multi-way Chromatin Interaction (MCI) analysis, including a visualization tool and a platform for identifying micro-domains with clustered single-molecule chromatin complexes. MCIBox is based on various clustering algorithms integrated with dimensionality reduction methods that can display multiplex chromatin interactions at single-molecule level, allowing users to explore chromatin extrusion patterns and super-enhancers regulation modes in transcription, and to identify single-molecule chromatin complexes that are clustered into micro-domains. Furthermore, MCIBox incorporates a two-dimensional kernel density estimation algorithm to identify micro-domains boundaries automatically. These micro-domains were stratified with distinctive signatures of transcription activity and contained different cell cycle associated genes. MCIBox could potentially distinguish the specificity of single-molecule chromatin interaction patterns in various phases of a cell cycle or cell types.

MCIBox: A Toolkit for Single-molecule Multi-way Chromatin Interaction Visualization and Micro-Domains Identification

The invention relates to pyropheophorbide-a methyl ether compounds, and a preparation method and application thereof. The compounds have the structure (I) in the specification. The invention relates to the fields of photodynamic therapy and photosensitive drugs (also called photosensitizers or photodynamic drugs), particularly a chlorophyll derivative photosensitizer and a preparation method thereof, and application of the chlorophyll derivative photosensitizer in the field of medicine. The photodynamic drug provided by the invention has the advantages of stable chemical properties, high solubility in water, and very high photodynamic activity, and can be used as a drug for the photodynamic diagnosis and treatment of tumors, retinal macular degeneration, actinic keratosis, nevus flammeus, condylomata acuminata and other diseases.

Meizhen Zheng

Papers

Multiplex chromatin interaction analysis by signal processing and statistical algorithms

Pore-C Simultaneously Captures Genome-wide Multi-way Chromatin Interaction and Associated DNA Methylation Status in Arabidopsis

Single nucleus and single molecule chromatin interaction assays

MCIBox: A Toolkit for Single-molecule Multi-way Chromatin Interaction Visualization and Micro-Domains Identification

Pyropheophorbide-a methyl ether compounds, and preparation method and application thereof