A5090127511- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- SARS-CoV-2 detection and testing
- Genomics and Phylogenetic Studies
- Legume Nitrogen Fixing Symbiosis
- SARS-CoV-2 and COVID-19 Research
- Gene expression and cancer classification
- Genetic Mapping and Diversity in Plants and Animals
- DNA and Nucleic Acid Chemistry
- Epigenetics and DNA Methylation
- Plant Molecular Biology Research
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Biosensors and Analytical Detection
- Advanced biosensing and bioanalysis techniques
- Hemoglobinopathies and Related Disorders
- Advanced Materials and Mechanics
- Microtubule and mitosis dynamics
- Energy Efficient Wireless Sensor Networks
- Genomic variations and chromosomal abnormalities
Massachusetts Institute of Technology
2015-2024
Altius Institute for Biomedical Sciences
2018-2020
Harvard University
2018-2020
Brigham and Women's Hospital
2018-2020
Broad Institute
2017-2020
Harvard–MIT Division of Health Sciences and Technology
2009-2019
IIT@MIT
2013-2018
Beth Israel Deaconess Medical Center
2017
Massachusetts General Hospital
2017
Cleveland Clinic
2017
We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. constructed spatial proximity maps human genome Hi-C at resolution 1 megabase. These confirm presence chromosome territories and small, gene-rich chromosomes. identified an additional level organization is characterized segregation open closed chromatin to form two genome-wide compartments. At megabase scale, conformation...
Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms TAD formation remain unclear. Here, we propose that loop extrusion underlies formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, show model produces TADs finer-scale features...
Mitotic chromosomes are among the most recognizable structures in cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across cell cycle revealed two distinct three-dimensional folding states of human genome. show that highly compartmentalized type-specific described previously nonsynchronous cells is restricted to interphase. In metaphase, we identified homogenous state locus-independent, common...
Significance Human DNA is 2 m long and folded into a 10-μm-sized cellular nucleus. Experiments have revealed two major features of genome organization: Segregation alternating active inactive regions compartments, formation compacted local domains. These were hypothesized to be formed by different mechanisms: Compartments can microphase separation domains active, motor-driven, loop extrusion. Here, we integrate these mechanisms polymer model show that their interplay coherently explains...
Caulobacter Chromosome Chromosomal DNA must be highly compacted to fit within the tiny volume of cell, while at same time it maintain a conformation that allows critical cellular processes access genome. Le et al. (p. 731 , published online 24 October) analyzed structure circular chromosome in prokaryote crescentus by using capture and deep-sequencing. Highly self-interacting regions (chromosomal interaction domains, or CIDs) were observed—similar topologically associated domains previously...
The three-dimensional folding of chromosomes compartmentalizes the genome and can bring distant functional elements, such as promoters enhancers, into close spatial proximity 2-6. Deciphering relationship between chromosome organization activity will aid in understanding genomic processes, like transcription replication. However, little is known about how fold. Microscopy unable to distinguish large numbers loci simultaneously or at high resolution. To date, detection chromosomal...
Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, revealed chromosomes animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin influence expression. Mechanisms underlie partitioning genome TADs remain poorly understood. To explore TAD in Drosophila melanogaster , we performed poly(A) + RNA-seq four cell lines...
Fertilization triggers assembly of higher-order chromatin structure from a condensed maternal and naïve paternal genome to generate totipotent embryo. Chromatin loops domains have been detected in mouse zygotes by single-nucleus Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when how embryonic conformations are assembled. Here, we investigated whether mechanism cohesin-dependent loop extrusion generates structures within the one-cell Using snHi-C knockout embryos, demonstrate that...
The mechanism by which chromatids and chromosomes are segregated during mitosis meiosis is a major puzzle of biology biophysics. Using polymer simulations chromosome dynamics, we show that single loop extrusion condensins can robustly compact, segregate disentangle chromosomes, arriving at individualized with morphology observed in vivo. Our model resolves the paradox topological simplification concomitant 'condensation', explains how enzymes few nanometers size able to control geometry...
Geoffrey Fudenberg1,5, Nezar Abdennur2,3,5, Maxim Imakaev3, Anton Goloborodko3,4 and Leonid A. Mirny3,4 1Gladstone Institute of Data Science Technology, University California, San Francisco, California 94158 2Computational Systems Biology Program, Massachusetts Cambridge, 02139 3Institute for Medical Engineering (IMES), 4Department Physics, Correspondence: geoff.fudenberg{at}gmail.com; leonid{at}mit.edu ↵5 These authors contributed equally to this work.
Chromosome conformation capture (3C) technologies reveal the incredible complexity of genome organization. Maps increasing size, depth, and resolution are now used to probe architecture across cell states, types, organisms. Larger datasets add challenges at each step computational analysis, from storage memory constraints researchers’ time; however, analysis tools that meet these increased resource demands have not kept pace. Furthermore, existing offer limited support for customizing...
Wastewater surveillance has emerged as a useful tool in the public health response to COVID-19 pandemic. While wastewater been applied at various scales monitor population-level dynamics, there is need for quantitative metrics interpret data context of trends. 24-hour composite samples were collected from March 2020 through May 2021 Massachusetts treatment plant and SARS-CoV-2 RNA concentrations measured using RT-qPCR. The relationship between copy numbers gene fragments clinical cases...
Abstract The 4D Nucleome (4DN) Network aims to elucidate the complex structure and organization of chromosomes in nucleus impact their disruption disease biology. We present 4DN Data Portal ( https://data.4dnucleome.org/ ), a repository for datasets generated network relevant external datasets. Datasets were with wide range experiments, including chromosome conformation capture assays such as Hi-C other innovative sequencing microscopy-based probing architecture. All together, data portal...
Abstract Chromosome conformation capture (3C) technologies reveal the incredible complexity of genome organization. Maps increasing size, depth, and resolution are now used to probe architecture across cell states, types, organisms. Larger datasets add challenges at each step computational analysis, from storage memory constraints researchers’ time; however, analysis tools that meet these increased resource demands have not kept pace. Furthermore, existing offer limited support for...
Abstract The relationships between chromosomal compartmentalization, chromatin state and function are poorly understood. Here by profiling long-range contact frequencies in HCT116 colon cancer cells, we distinguish three silent states, comprising two types of heterochromatin a enriched for H3K9me2 H2A.Z that exhibits neutral three-dimensional interaction preferences which, to our knowledge, has not previously been characterized. We find marked H3K9me3, HP1α HP1β correlates with strong...
Wastewater-based epidemiology has emerged as a promising technology for population-level surveillance of COVID-19. In this study, we present results large nationwide SARS-CoV-2 wastewater monitoring system in the United States. We profile 55 locations with at least six months sampling from April 2020 to May 2021. These represent more than 12 million individuals across 19 states. Samples were collected approximately weekly by treatment utilities part regular service and analyzed RNA...
Abstract The field of 3D genome organization produces large amounts sequencing data from Hi-C and a rapidly-expanding set other chromosome conformation protocols (3C+). Massive heterogeneous 3C+ require high-performance flexible processing sequenced reads into contact pairs. To meet these challenges, we present pairtools – suite tools for extraction data. Pairtools provides modular command-line interface (CLI) that can be flexibly chained pipelines. both crucial core as well auxiliary...