Search NASA⌕ Search

SEARCH · Search NASA

Results for “single-cell genomics”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Spatially structured bacterial interactions alter algal carbon flow to bacteria

Phytoplankton account for nearly half of global photosynthetic carbon fixation, and the fate of that carbon is regulated in large part by microbial food web processing. We currently lack a mechanistic understanding of how interactions among heterotrophic bacteria impact the fate of photosynthetically fixed carbon. Here, we used a set of bacterial isolates capable of growing on exudates from the diatom Phaeodactylum tricornutum to investigate how bacteria-bacteria interactions affect the balance between exudate remineralization and incorporation into biomass. With exometabolomics and genome-scale metabolic modeling, we estimated the degree of resource competition between bacterial pairs. In a sequential spent media experiment, we found that pairwise interactions were more beneficial than predicted based on resource competition alone, and 30% exhibited facilitative interactions. To link this to carbon fate, we used single-cell isotope tracing in a custom cultivation system to compare the impact of different "primary" bacterial strains in close proximity to live P. tricornutum on a distal "secondary" strain. We found that a primary strain with a high degree of competition decreased secondary strain carbon drawdown by 51% at the single-cell level, providing a quantitative metric for the "cost" of competition on algal carbon fate. Additionally, a primary strain classified as facilitative based on sequential interactions increased total algal-derived carbon assimilation by 7.6 times, integrated over all members, compared to the competitive primary strain. Our findings suggest that the degree of interaction between bacteria along a spectrum from competitive to facilitative is directly linked to algal carbon drawdown.

genome-scale metabolic model↗
DOE OSTI2024

Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here, we present the culmination of the efforts of the modENCODE (model organism Encyclopedia of DNA Elements) and modERN (model organism Encyclopedia of Regulatory Networks) consortia to systematically assay TF binding events in vivo in two major model organisms,Drosophila melanogaster(fly) andCaenorhabditis elegans(worm). These data sets comprise 605 TFs identifying 3.6 M sites in the fly and 356 TFs identifying 0.9 M sites in the worm, and represent the majority of the regulatory space in each genome. We demonstrate that TFs associate with chromatin in clusters termed “metapeaks,” that larger metapeaks have characteristics of high-occupancy target (HOT) regions, and that the importance of consensus sequence motifs bound by TFs depends on metapeak size and complexity. Combining ChIP-seq data with single-cell RNA-seq data in a machine-learning model identifies TFs with a prominent role in promoting target gene expression in specific cell types, even differentiating between parent–daughter cells during embryogenesis. These data are a rich resource for the community that should fuel and guide future investigations into TF function. To facilitate data accessibility and utility, all strains expressing green fluorescent protein (GFP)-tagged TFs are available at the stock centers for each organism. The chromatin immunoprecipitation sequencing data are available through the ENCODE Data Coordinating Center, GEO, and through a direct interface that provides rapid access to processed data sets and summary analyses, as well as widgets to probe the cell-type-specific TF–target relationships.

Biochemistry & Molecular Biology↗
DOE OSTI2022

Improved high-throughput screening technique to rapidly isolate Chlamydomonas transformants expressing recombinant proteins

Abstract The single-celled eukaryotic green alga Chlamydomonas reinhardtii has long been a model system for developing genetic tools for algae, and is also considered a potential platform for the production of high-value recombinant proteins. Identifying transformants with high levels of recombinant protein expression has been a challenge in this organism, as random integration of transgenes into the nuclear genome leads to low frequency of cell lines with high gene expression. Here, we describe the design of an optimized vector for the expression of recombinant proteins in Chlamydomonas , that when transformed and screened using a dual antibiotic selection, followed by screening using fluorescence activated cell sorting (FACS), permits rapid identification and isolation of microalgal transformants with high expression of a recombinant protein. This process greatly reduces the time required for the screening process, and can produce large populations of recombinant algae transformants with between 60 and 100% of cells producing the recombinant protein of interest, in as little as 3 weeks, that can then be used for whole population sequencing or individual clone analysis. Utilizing this new vector and high-throughput screening (HTS) process resulted in an order of magnitude improvement over existing methods, which normally produced under 1% of algae transformants expressing the protein of interest. This process can be applied to other algal strains and recombinant proteins to enhance screening efficiency, thereby speeding up the discovery and development of algal-derived recombinant protein products. Key points • A protein expression vector using double-antibiotic resistance genes was designed • Double antibiotic selection causes fewer colonies with more positive for phenotype • Coupling the new vector with FACS improves microalgal screening efficiency > 60%

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Time-series metagenomics reveals changing protistan ecology of a temperate dimictic lake

Abstract Background Protists, single-celled eukaryotic organisms, are critical to food web ecology, contributing to primary productivity and connecting small bacteria and archaea to higher trophic levels. Lake Mendota is a large, eutrophic natural lake that is a Long-Term Ecological Research site and among the world’s best-studied freshwater systems. Metagenomic samples have been collected and shotgun sequenced from Lake Mendota for the last 20 years. Here, we analyze this comprehensive time series to infer changes to the structure and function of the protistan community and to hypothesize about their interactions with bacteria. Results Based on small subunit rRNA genes extracted from the metagenomes and metagenome-assembled genomes of microeukaryotes, we identify shifts in the eukaryotic phytoplankton community over time, which we predict to be a consequence of reduced zooplankton grazing pressures after the invasion of a invasive predator (the spiny water flea) to the lake. The metagenomic data also reveal the presence of the spiny water flea and the zebra mussel, a second invasive species to Lake Mendota, prior to their visual identification during routine monitoring. Furthermore, we use species co-occurrence and co-abundance analysis to connect the protistan community with bacterial taxa. Correlation analysis suggests that protists and bacteria may interact or respond similarly to environmental conditions. Cryptophytes declined in the second decade of the timeseries, while many alveolate groups (e.g., ciliates and dinoflagellates) and diatoms increased in abundance, changes that have implications for food web efficiency in Lake Mendota. Conclusions We demonstrate that metagenomic sequence-based community analysis can complement existing efforts to monitor protists in Lake Mendota based on microscopy-based count surveys. We observed patterns of seasonal abundance in microeukaryotes in Lake Mendota that corroborated expectations from other systems, including high abundance of cryptophytes in winter and diatoms in fall and spring, but with much higher resolution than previous surveys. Our study identified long-term changes in the abundance of eukaryotic microbes and provided context for the known establishment of an invasive species that catalyzes a trophic cascade involving protists. Our findings are important for decoding potential long-term consequences of human interventions, including invasive species introduction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Mass Spectrometry–Based Proteogenomics: New Therapeutic Opportunities for Precision Medicine

Proteogenomics refers to the integration of comprehensive genomic, transcriptomic, and proteomic measurements from the same samples with the goal of fully understanding the regulatory processes converting genotypes to phenotypes, often with an emphasis on gaining a deeper understanding of disease processes. Although specific genetic mutations have long been known to drive the development of multiple cancers, gene mutations alone do not always predict prognosis or response to targeted therapy. The benefit of proteogenomics research is that information obtained from proteins and their corresponding pathways provides insight into therapeutic targets that can complement genomic information by providing an additional dimension regarding the underlying mechanisms and pathophysiology of tumors. This review describes the novel insights into tumor biology and drug resistance derived from proteogenomic analysis while highlighting the clinical potential of proteogenomic observations and advances in technique and analysis tools.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Spatial Proteomics towards cellular Resolution

Introduction: Spatial biology is an emerging interdisciplinary field facilitating biological discoveries through the use of spatial omics technologies. Recent advancements in spatial transcriptomics, spatial genomics (e.g. genetic mutations and epigenetic marks), multiplexed immunofluorescence, and spatial metabolomics/lipidomics have enabled high-resolution spatial profiling of gene expression, genetic variation, protein expression, and metabolites/lipids profiles in tissue. These developments contribute to a deeper understanding of the spatial organization within tissue microenvironments at the molecular level. Areas covered: This report provides an overview of the untargeted, bottom-up mass spectrometry (MS)-based spatial proteomics workflow. It highlights recent progress in tissue dissection, sample processing, bioinformatics, and liquid chromatography (LC)-MS technologies that are advancing spatial proteomics toward cellular resolution. Expert opinion: The field of untargeted MS-based spatial proteomics is rapidly evolving and holds great promise. To fully realize the potential of spatial proteomics, it is critical to advance data analysis and develop automated and intelligent tissue dissection at the cellular or subcellular level, along with high-throughput LC-MS analyses of thousands of samples. In conclusion, achieving these goals will necessitate significant advancements in tissue dissection technologies, LC-MS instrumentation, and computational tools.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Deep Learning‐Assisted Automated Single Cell Electroporation Platform for Effective Genetic Manipulation of Hard‐to‐Transfect Cells

Abstract Genome engineering of cells using CRISPR/Cas systems has opened new avenues for pharmacological screening and investigating the molecular mechanisms of disease. A critical step in many such studies is the intracellular delivery of the gene editing machinery and the subsequent manipulation of cells. However, these workflows often involve processes such as bulk electroporation for intracellular delivery and fluorescence activated cell sorting for cell isolation that can be harsh to sensitive cell types such as human‐induced pluripotent stem cells (hiPSCs). This often leads to poor viability and low overall efficacy, requiring the use of large starting samples. In this work, a fully automated version of the nanofountain probe electroporation (NFP‐E) system, a nanopipette‐based single‐cell electroporation method is presented that provides superior cell viability and efficiency compared to traditional methods. The automated system utilizes a deep convolutional network to identify cell locations and a cell‐nanopipette contact algorithm to position the nanopipette over each cell for the application of electroporation pulses. The automated NFP‐E is combined with microconfinement arrays for cell isolation to demonstrate a workflow that can be used for CRISPR/Cas9 gene editing and cell tracking with potential applications in screening studies and isogenic cell line generation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Advances in mass spectrometry-enabled multiomics at single-cell resolution

We report biological organisms are multifaceted, intricate systems where slight perturbations can result in extensive changes in gene expression, protein abundance and/or activity, and metabolic flux. These changes occur at different timescales, spatially across cells of heterogeneous origins, and within single-cells. Hence, multimodal measurements at the smallest biological scales are necessary to capture dynamic changes in heterogeneous biological systems. Of the analytical techniques used to measure biomolecules, mass spectrometry (MS) has proven to be a powerful option due to its sensitivity, robustness, and flexibility with regard to the breadth of biomolecules that can be analyzed. Recently, many studies have coupled MS to other analytical techniques with the goal of measuring multiple modalities from the same single-cell. It is with these concepts in mind that we focus this review on MS-enabled multiomic measurements at single-cell or near-single- cell resolution.

47 OTHER INSTRUMENTATION↗
DOE OSTI2022

Dynamic and single cell characterization of a CRISPR-interference toolset in Pseudomonas putida KT2440 for β-ketoadipate production from p -coumarate

We report Pseudomonas putida KT2440 is a well-studied bacterium for the conversion of lignin-derived aromatic compounds to bioproducts. The development of advanced genetic tools in P. putida has reduced the turnaround time for hypothesis testing and enabled the construction of strains capable of producing various products of interest. Here, we evaluate an inducible CRISPR-interference (CRISPRi) toolset on fluorescent, essential, and metabolic targets. Nuclease-deficient Cas9 (dCas9) expressed with the arabinose (8K)-inducible promoter was shown to be tightly regulated across various media conditions and when targeting essential genes. In addition to bulk growth data, single cell time lapse microscopy was conducted, which revealed intrinsic heterogeneity in knockdown rate within an isoclonal population. The dynamics of knockdown were studied across genomic targets in exponentially-growing cells, revealing a universal 1.75 ± 0.38 hour quiescent phase after induction where 1.5 ± 0.35 doublings occur before a phenotypic response is observed. To demonstrate application of this CRISPRi toolset, β-ketoadipate, a monomer for performance-advantaged nylon, was produced at a 4.39 ± 0.5 g/L and yield of 0.76 ± 0.10 mol/mol from p-coumarate, a hydroxycinnamic acid that can be derived from grasses. These cultivation metrics were achieved by using the higher strength IPTG (1K)-inducible promoter to knockdown the pcaIJ operon in the βKA pathway during early exponential phase. This allowed the majority of the carbon to be shunted into the desired product while eliminating the need for a supplemental carbon and energy source to support growth and maintenance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Single-cell isotope tracing reveals functional guilds of bacteria associated with the diatom Phaeodactylum tricornutum

Abstract Bacterial remineralization of algal organic matter fuels algal growth but is rarely quantified. Consequently, we cannot currently predict whether some bacterial taxa may provide more remineralized nutrients to algae than others. Here, we quantified bacterial incorporation of algal-derived complex dissolved organic carbon and nitrogen and algal incorporation of remineralized carbon and nitrogen in fifteen bacterial co-cultures growing with the diatom Phaeodactylum tricornutum at the single-cell level using isotope tracing and nanoSIMS. We found unexpected strain-to-strain and cell-to-cell variability in net carbon and nitrogen incorporation, including non-ubiquitous complex organic nitrogen utilization and remineralization. We used these data to identify three distinct functional guilds of metabolic interactions, which we termed macromolecule remineralizers, macromolecule users, and small-molecule users, the latter exhibiting efficient growth under low carbon availability. The functional guilds were not linked to phylogeny and could not be elucidated strictly from metabolic capacity as predicted by comparative genomics, highlighting the need for direct activity-based measurements in ecological studies of microbial metabolic interactions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Dynamic enhancer landscapes in human craniofacial development

The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Spatial co-transcriptomics reveals discrete stages of the arbuscular mycorrhizal symbiosis

Abstract The symbiotic interaction of plants with arbuscular mycorrhizal (AM) fungi is ancient and widespread. Plants provide AM fungi with carbon in exchange for nutrients and water, making this interaction a prime target for crop improvement. However, plant–fungal interactions are restricted to a small subset of root cells, precluding the application of most conventional functional genomic techniques to study the molecular bases of these interactions. Here we used single-nucleus and spatial RNA sequencing to explore both Medicago truncatula and Rhizophagus irregularis transcriptomes in AM symbiosis at cellular and spatial resolution. Integrated, spatially registered single-cell maps revealed infected and uninfected plant root cell types. We observed that cortex cells exhibit distinct transcriptome profiles during different stages of colonization by AM fungi, indicating dynamic interplay between both organisms during establishment of the cellular interface enabling successful symbiosis. Our study provides insight into a symbiotic relationship of major agricultural and environmental importance and demonstrates a paradigm combining single-cell and spatial transcriptomics for the analysis of complex organismal interactions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Multiomics and deep learning dissect regulatory syntax in human development

Transcription factors establish cell identity during development by binding regulatory DNA in a sequence-specific manner, often promoting local chromatin accessibility and regulating gene expression1. Mapping accessible chromatin offers critical insights into transcriptional control, but available datasets for human development are restricted to bulk tissue, single organs or single modalities2. Here we present the Human Development Multiomic Atlas, a single-cell atlas of chromatin accessibility and gene expression from 817,740 fetal cells across 12 organs, spanning 203 cell types and more than 1 million candidate cis-regulatory elements, many of which exhibit organ-specific in vivo enhancer activity. Deep learning models trained to predict accessibility from local DNA sequence unravel a comprehensive lexicon of motifs that influence accessibility, including composite motifs exhibiting distinct syntactic constraints that are predicted to mediate transcription factor cooperativity. We identify ‘hard’ syntactic rules requiring precise motif spacing and orientation, ‘soft’ rules allowing flexible motif arrangements, and ubiquitous motifs inhibiting accessibility. Model-based interpretation of genetic variants reveals that disruption of motifs with positive and negative effects is associated with concordant effects on gene expression. Our work delineates how motif syntax governs cell-type-specific chromatin accessibility and provides a foundational resource for decoding cis-regulatory logic and interpreting genetic variation during human development.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA

Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the most frequently genomically altered driver oncogenes, generates an immunogenic public NeoAg. Using this strategy, we developed a panel of TCRs that recognize an endogenously processed neopeptide encompassing a common PIK3CA hotspot mutation restricted by the prevalent human leukocyte antigen (HLA)-A*03:01 allele. Mechanistically, immunogenicity to this public NeoAg arises from enhanced neopeptide/HLA complex stability caused by a preferred HLA anchor substitution. Structural studies indicated that the HLA-bound neopeptide presents a comparatively ‘featureless’ surface dominated by the peptide’s backbone. To bind this epitope with high specificity and affinity, we discovered that a lead TCR clinical candidate engages the neopeptide through an extended interface facilitated by an unusually long CDR3β loop. In patients with diverse malignancies, we observed NeoAg clonal conservation and spontaneous immunogenicity to the neoepitope. Finally, adoptive transfer of TCR-engineered T cells led to tumor regression in vivo in mice bearing PIK3CA-mutant tumors but not wild-type PIK3CA tumors. Together, these findings establish the immunogenicity and therapeutic potential of a mutant PIK3CA-derived public NeoAg.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

High-throughput single-cell transcriptomics of bacteria using combinatorial barcoding

Microbial split-pool ligation transcriptomics (microSPLiT) is a high-throughput single-cell RNA sequencing method for bacteria. With four combinatorial barcoding rounds, microSPLiT can profile transcriptional states in hundreds of thousands of Gram-negative and Gram-positive bacteria in a single experiment without specialized equipment. As bacterial samples are fixed and permeabilized before barcoding, they can be collected and stored ahead of time. During the first barcoding round, the fixed and permeabilized bacteria are distributed into a 96-well plate, where their transcripts are reverse transcribed into cDNA and labeled with the first well-specific barcode inside the cells. The cells are mixed and redistributed two more times into new 96-well plates, where the second and third barcodes are appended to the cDNA via in-cell ligation reactions. Finally, the cells are mixed and divided into aliquot sub-libraries, which can be stored until future use or prepared for sequencing with the addition of a fourth barcode. It takes 4 days to generate sequencing-ready libraries, including 1 day for collection and overnight fixation of samples. Here, the standard plate setup enables single-cell transcriptional profiling of up to 1 million bacterial cells and up to 96 samples in a single barcoding experiment, with the possibility of expansion by adding barcoding rounds. The protocol requires experience in basic molecular biology techniques, handling of bacterial samples and preparation of DNA libraries for next-generation sequencing. It can be performed by experienced undergraduate or graduate students. Data analysis requires access to computing resources, familiarity with Unix command line and basic experience with Python or R.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A maize semi-dwarf mutant reveals a GRAS transcription factor involved in brassinosteroid signaling

Brassinosteroids (BR) and gibberellins (GA) regulate plant height and leaf angle in maize (Zea mays). Mutants with defects in BR or GA biosynthesis or signaling identify components of these pathways and enhance our knowledge about plant growth and development. In this study, we characterized three recessive mutant alleles of GRAS transcription factor 42 (gras42) in maize, a GRAS transcription factor gene orthologous to the DWARF AND LOW TILLERING (DLT) gene of rice (Oryza sativa). These maize mutants exhibited semi-dwarf stature, shorter and wider leaves, and more upright leaf angle. Transcriptome analysis revealed a role for GRAS42 as a determinant of BR signaling. Analysis of the expression consequences from loss of GRAS42 in the gras42-mu1021149 mutant indicated a weak loss of BR signaling in the mutant, consistent with its previously demonstrated role in BR signaling in rice. Loss of BR signaling was also evident by the enhancement of weak BR biosynthetic mutant alleles in double mutants of nana plant1-1 and gras42-mu1021149. The gras42-mu1021149 mutant had little effect on GA-regulated gene expression, suggesting that GRAS42 is not a regulator of core GA signaling genes in maize. Single-cell expression data identified gras42 expressed among cells in the G2/M phase of the cell cycle consistent with its previously demonstrated role in cell cycle gene expression in Arabidopsis (Arabidopsis thaliana). Cis-acting natural variation controlling GRAS42 transcript accumulation was identified by expression genome-wide association study (eGWAS) in maize. Our results demonstrate a conserved role for GRAS42/SCARECROW-LIKE 28 (SCL28)/DLT in BR signaling, clarify the role of this gene in GA signaling, and suggest mechanisms of tillering and leaf angle control by BR.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Proposed minimal standards for description of methanogenic archaea

Methanogenic archaea are a diverse, polyphyletic group of strictly anaerobic prokaryotes capable of producing methane as their primary metabolic product. It has been over three decades since minimal standards for their taxonomic description have been proposed. In light of advancements in technology and amendments in systematic microbiology, revision of the older criteria for taxonomic description is essential. Most of the previously recommended minimum standards regarding phenotypic characterization of pure cultures are maintained. Electron microscopy and chemotaxonomic methods like whole-cell protein and lipid analysis are desirable but not required. Because of advancements in DNA sequencing technologies, obtaining a complete or draft whole genome sequence for type strains and its deposition in a public database are now mandatory. Genomic data should be used for rigorous comparison to close relatives using overall genome related indices such as average nucleotide identity and digital DNA–DNA hybridization. Phylogenetic analysis of the 16S rRNA gene is also required and can be supplemented by phylogenies of the mcrA gene and phylogenomic analysis using multiple conserved, single-copy marker genes. Additionally, it is now established that culture purity is not essential for studying prokaryotes, and description of Candidatus methanogenic taxa using single-cell or metagenomics along with other appropriate criteria is a viable alternative. The revisions to the minimal criteria proposed here by the members of the Subcommittee on the Taxonomy of Methanogenic Archaea of the International Committee on Systematics of Prokaryotes should allow for rigorous yet practical taxonomic description of these important and diverse microbes.

Microbiology↗
DOE OSTI2025

Chromatin structures from integrated AI and polymer physics model

The physical organization of the genome in three-dimensional space regulates many biological processes, including gene expression and cell differentiation. Three-dimensional characterization of genome structure is critical to understanding these biological processes. Direct experimental measurements of genome structure are challenging; computational models of chromatin structure are therefore necessary. We develop an approach that combines a particle-based chromatin polymer model, molecular simulation, and machine learning to efficiently and accurately estimate chromatin structure fromindirectmeasures of genome structure. More specifically, we introduce a new approach where the interaction parameters of the polymer model are extracted from experimental Hi-C data using a graph neural network (GNN). We train the GNN on simulated data from the underlying polymer model, avoiding the need for large quantities of experimental data. The resulting approach accurately estimates chromatin structures across all chromosomes and across several experimental cell lines despite being trained almost exclusively on simulated data. The proposed approach can be viewed as a general framework for combining physical modeling with machine learning, and it could be extended to integrate additional biological data modalities. Ultimately, we achieve accurate and high-throughput estimations of chromatin structure from Hi-C data, which will be necessary as experimental methodologies, such as single-cell Hi-C, improve.

Biochemistry & Molecular Biology↗