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At least 1,783 records · Page 99
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

A modERN resource: identification of Drosophila transcription factor candidate target genes using RNAi

Transcription factors (TFs) play a key role in development and in cellular responses to the environment by activating or repressing the transcription of target genes in precise spatial and temporal patterns. In order to develop a catalog of target genes of Drosophila melanogaster TFs, the modERN consortium systematically knocked down the expression of TFs using RNAi in whole embryos followed by RNA-seq. We generated data for 45 TFs which have 18 different DNA-binding domains and are expressed in 15 of the 16 organ systems. The range of inactivation of the targeted TFs by RNAi ranged from log2fold change -3.52 to +0.49. The TFs also showed remarkable heterogeneity in the numbers of candidate target genes identified, with some generating thousands of candidates and others only tens. We present detailed analysis from five experiments, including those for three TFs that have been the focus of previous functional studies (ERR, sens, and zfh2) and two previously uncharacterized TFs (sens-2 and CG32006), as well as short vignettes for selected additional experiments to illustrate the utility of this resource. The RNA-seq datasets are available through the ENCODE DCC (http://encodeproject.org) and the Sequence Read Archive (SRA). TF and target gene expression patterns can be found here: https://insitu.fruitfly.org. These studies provide data that facilitate scientific inquiries into the functions of individual TFs in key developmental, metabolic, defensive, and homeostatic regulatory pathways, as well as provide a broader perspective on how individual TFs work together in local networks during embryogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus

Mathematical models explain how antivirals control viral infections. Hepatitis C virus (HCV) treatment results in at least 2 phases of decline in viremia. Here, the first phase reflects clearance of rapidly produced virions. The second phase is hypothesized to derive from loss of infected cells but has been challenging to prove. Using single-cell methods, we quantified the number of hepatitis C virus (HCV)-infected hepatocytes in liver biopsies taken before and within 7 days of initiating direct-acting antivirals (DAAs) in a double-blinded randomized controlled trial testing 2 (sofosbuvir-velpatasvir) versus 3 (sofosbuvir-velpatasvir-voxilaprevir) DAAs. We employed thousands of intrahepatic measurements in 10 persons with chronic genotype 1a HCV infection: median proportion of infected hepatocytes declined from 11.3% (range, 1.3%–59%) to 0.6% (range, <0.3%–5.8%), a loss of 75%–95% infected hepatocytes. Plasma viremia correlated with numbers of HCV-infected hepatocytes (r = 0.77; P < .0001). Second-phase plasma dynamics and changes in infected hepatocytes were indistinct (P = .16), demonstrating that second-phase viral dynamics derive from loss of infected cells. DAAs led to a decline in intracellular HCV RNA and interferon-stimulated gene expression (P < .05 for both). We proved that second-phase viral dynamics reflect decay of intrahepatic burden of HCV, partly due to clearance of HCV RNA from hepatocytes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Regional epithelial cell diversity in the small intestine of pigs

Abstract Understanding regional distribution and specialization of small intestinal epithelial cells is crucial for developing methods to control appetite, stress, and nutrient uptake in swine. To establish a better understanding of specific epithelial cells found across different regions of the small intestine in pigs, we utilized single-cell RNA sequencing (scRNA-seq) to recover and analyze epithelial cells from duodenum, jejunum, and ileum. Cells identified included crypt cells, enterocytes, BEST4 enterocytes, goblet cells, and enteroendocrine (EE) cells. EE cells were divided into two subsets based on the level of expression of the EE lineage commitment gene, NEUROD1. NEUROD1hi EE cells had minimal expression of hormone-encoding genes and were dissimilar to EE cells in humans and mice, indicating a subset of EE cells unique to pigs. Recently discovered BEST4 enterocytes were detected in both crypts and villi throughout the small intestine via in situ staining, unlike in humans, where BEST4 enterocytes are found only in small intestinal villi. Proximal-to-distal gradients of expression were noted for hormone-encoding genes in EE cells and nutrient transport genes in enterocytes via scRNA-seq, demonstrating regional specialization. Regional gene expression in EE cells and enterocytes was validated via quantitative PCR (qPCR) analysis of RNA isolated from epithelial cells of different small intestinal locations. Though many genes had similar patterns of regional expression when assessed by qPCR of total epithelial cells, some regional expression was only detected via scRNA-seq, highlighting advantages of scRNA-seq to deconvolute cell type-specific regional gene expression when compared to analysis of bulk samples. Overall, results provide new information on regional localization and transcriptional profiles of epithelial cells in the pig small intestine.

Agriculture↗
DOE OSTI2015

Effects of PHENYLALANINE AMMONIA LYASE ( PAL ) knockdown on cell wall composition, biomass digestibility, and biotic and abiotic stress responses in Brachypodium

The phenylpropanoid pathway in plants synthesizes a variety of structural and defence compounds, and is an important target in efforts to reduce cell wall lignin for improved biomass conversion to biofuels. Little is known concerning the trade-offs in grasses when perturbing the function of the first gene family in the pathway, PHENYLALANINE AMMONIA LYASE ( PAL ). Therefore, PAL isoforms in the model grass Brachypodium distachyon were targeted, by RNA interference (RNAi), and large reductions (up to 85%) in stem tissue transcript abundance for two of the eight putative BdPAL genes were identified. The cell walls of stems of BdPAL -knockdown plants had reductions of 43% in lignin and 57% in cell wall-bound ferulate, and a nearly 2-fold increase in the amounts of polysaccharide-derived carbohydrates released by thermochemical and hydrolytic enzymic partial digestion. PAL -knockdown plants exhibited delayed development and reduced root growth, along with increased susceptibilities to the fungal pathogens Fusarium culmorum and Magnaporthe oryzae . Surprisingly, these plants generally had wild-type (WT) resistances to caterpillar herbivory, drought, and ultraviolet light. RNA sequencing analyses revealed that the expression of genes associated with stress responses including ethylene biosynthesis and signalling were significantly altered in PAL knocked-down plants under non-challenging conditions. These data reveal that, although an attenuation of the phenylpropanoid pathway increases carbohydrate availability for biofuel, it can adversely affect plant growth and disease resistance to fungal pathogens. Lastly, the data identify notable differences between the stress responses of these monocot pal mutants versus Arabidopsis (a dicot) pal mutants and provide insights into the challenges that may arise when deploying phenylpropanoid pathway-altered bioenergy crops.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Mo than meets the eye: genomic insights into molybdoenzyme diversity of Seleniivibrio woodruffii strain S4T

Abstract Seleniivibrio woodruffii strain S4T is an obligate anaerobe belonging to the phylum Deferribacterota. It was isolated for its ability to respire selenate and was also found to respire arsenate. The high-quality draft genome of this bacterium is 2.9 Mbp, has a G+C content of 48%, 2762 predicted genes of which 2709 are protein-coding, and 53 RNA genes. An analysis of the genome focusing on the genes encoding for molybdenum-containing enzymes (molybdoenzymes) uncovered a remarkable number of genes encoding for members of the dimethylsulfoxide reductase family of proteins (DMSOR), including putative reductases for selenate and arsenate respiration, as well as genes for nitrogen fixation. Respiratory molybdoenzymes catalyze redox reactions that transfer electrons to a variety of substrates that can act as terminal electron acceptors for energy generation. Seleniivibrio woodruffii strain S4T also has essential genes for molybdate transporters and the biosynthesis of the molybdopterin guanine dinucleotide cofactors characteristic of the active centers of DMSORs. Phylogenetic analysis revealed candidate respiratory DMSORs spanning nine subfamilies encoded within the genome. Our analysis revealed the untapped potential of this interesting microorganism and expanded our knowledge of molybdoenzyme co-occurrence.

Louie, Tiffany S.↗
DOE OSTI2020

Biochemical and structural basis for YTH domain of human YTHDC1 binding to methylated adenine in DNA

The recently characterized mammalian writer (methyltransferase) and eraser (demethylase) of the DNA N6-methyladenine (N6mA) methyl mark act on single-stranded (ss) and transiently-unpaired DNA. As YTH domain-containing proteins bind N6mA-containing RNA in mammalian cells, we investigated whether mammalian YTH domains are also methyl mark readers of N6mA DNA. Here, we show that the YTH domain of YTHDC1 (known to localize in the nucleus) binds ssDNA containing N6mA, with a 10 nM dissociation constant. This binding is stronger by a factor of 5 than in an RNA context, tested under the same conditions. However, the YTH domains of YTHDF2 and YTHDF1 (predominantly cytoplasmic) exhibited the opposite effect with ~1.5–2× stronger binding to ssRNA containing N6mA than to the corresponding DNA. We determined two structures of the YTH domain of YTHDC1 in complex with N6mA-containing ssDNA, which illustrated that YTHDC1 binds the methylated adenine in a single-stranded region flanked by duplexed DNA. We discuss the hypothesis that the writer-reader-eraser of N6mA-containining ssDNA is associated with maintaining genome stability. Structural comparison of YTH and SRA domains (the latter a DNA 5-methylcytosine reader) revealed them to be diverse members of a larger family of DNA/RNA modification readers, apparently having originated from bacterial modification-dependent restriction enzymes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation

Abstract Liquid–liquid phase separation underlies the membrane-less compartmentalization of cells. Intrinsically disordered low-complexity domains (LCDs) often mediate phase separation, but how their phase behavior is modulated by folded domains is incompletely understood. Here, we interrogate the interplay between folded and disordered domains of the RNA-binding protein hnRNPA1. The LCD of hnRNPA1 is sufficient for mediating phase separation in vitro. However, we show that the folded RRM domains and a folded solubility-tag modify the phase behavior, even in the absence of RNA. Notably, the presence of the folded domains reverses the salt dependence of the driving force for phase separation relative to the LCD alone. Small-angle X-ray scattering experiments and coarse-grained MD simulations show that the LCD interacts transiently with the RRMs and/or the solubility-tag in a salt-sensitive manner, providing a mechanistic explanation for the observed salt-dependent phase separation. These data point to two effects from the folded domains: (i) electrostatically-mediated interactions that compact hnRNPA1 and contribute to phase separation and (ii) increased solubility at higher ionic strengths mediated by the folded domains. The interplay between disordered and folded domains can modify the dependence of phase behavior on solution conditions and can obscure signatures of physicochemical interactions underlying phase separation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity

HIV-1 reverse transcription initiates at the primer binding site (PBS) in the viral genomic RNA (gRNA). Although the structure of the PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, the proper folding of the PBS-segment during gRNA packaging is important as it ensures loading of beneficial host factors. DHX9/RNA helicase A (RHA) is recruited to gRNA to enhance the processivity of reverse transcriptase. Because the molecular details of the interactions have yet to be defined, we solved the solution structure of the PBS-segment preferentially bound by RHA. Evidence is provided that PBS-segment adopts a previously undefined adenosine-rich three-way junction structure encompassing the primer activation stem (PAS), tRNA-like element (TLE) and tRNA annealing arm. Disruption of the PBS-segment three-way junction structure diminished reverse transcription products and led to reduced viral infectivity. Because of the existence of the tRNA annealing arm, the TLE and PAS form a bent helical structure that undergoes shape-dependent recognition by RHA double-stranded RNA binding domain 1 (dsRBD1). Mutagenesis and phylogenetic analyses provide evidence for conservation of the PBS-segment three-way junction structure that is preferentially bound by RHA in support of efficient reverse transcription, the hallmark step of HIV-1 replication.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes

Abstract CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities. We present CasPEDIA (http://caspedia.org), the Cas Protein Effector Database of Information and Assessment, a curated encyclopedia that integrates enzymatic classification for hundreds of different Cas enzymes across 27 phylogenetic groups spanning the Cas9, Cas12 and Cas13 families, as well as evolutionarily related IscB and TnpB proteins. All enzymes in CasPEDIA were annotated with a standard workflow based on their primary nuclease activity, target requirements and guide-RNA design constraints. Our functional classification scheme, CasID, is described alongside current phylogenetic classification, allowing users to search related orthologs by enzymatic function and sequence similarity. CasPEDIA is a comprehensive data portal that summarizes and contextualizes enzymatic properties of widely used Cas enzymes, equipping users with valuable resources to foster biotechnological development. CasPEDIA complements phylogenetic Cas nomenclature and enables researchers to leverage the multi-faceted nucleic-acid targeting rules of diverse Class 2 Cas enzymes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Sparsomycin inhibits translation through a conserved mechanism across all domains of life

Abstract Sparsomycin (SPA) is a broad-spectrum inhibitor of protein synthesis with activity across all three domains of life. Although SPA has long been known to target the ribosomal peptidyl transferase center (PTC), previous structural studies suggested that SPA binds differently to bacterial ribosomes compared to their archaeal and eukaryotic counterparts—an unexpected conclusion given the high evolutionary conservation of the ribosomal catalytic center. Here, we show that SPA inhibits a majority of elongation-competent bacterial ribosomal complexes and present X-ray crystal structures of Thermus thermophilus 70S ribosomes stalled by SPA at the initiation and early elongation stages of translation. These structures reveal that SPA binds to the bacterial ribosome in a manner essentially identical to that observed in archaeal and eukaryotic ribosomes, establishing a unified structural mechanism of SPA action across all domains of life. In this conserved binding mode, SPA occupies the A-site cleft of the PTC and forms an extensive network of interactions with universally conserved ribosomal RNA nucleotides and the CCA-end of the P-site transfer RNA (tRNA), thereby stabilizing the peptidyl-tRNA substrate while sterically blocking accommodation of an incoming aminoacyl-tRNA. By clarifying the mode of action of SPA on the bacterial ribosome, our work provides a structural framework for the rational design of SPA derivatives with improved potency and bacterial specificity.

Paranjpe, Madhura N [Department of Biological Scie↗
DOE OSTI2013

Hepatitis C virus 3'UTR regulates viral translation through direct interactions with the host translation machinery

The 3' untranslated region (3' UTR) of hepatitis C virus (HCV) messenger RNA stimulates viral translation by an undetermined mechanism. We identified a high affinity interaction, conserved among different HCV genotypes, between the HCV 3' UTR and the host ribosome. The 3' UTR interacts with 40S ribosomal subunit proteins residing primarily in a localized region on the 40S solvent-accessible surface near the messenger RNA entry and exit sites. This region partially overlaps with the site where the HCV internal ribosome entry site was found to bind, with the internal ribosome entry site-40S subunit interaction being dominant. Despite its ability to bind to 40S subunits independently, the HCV 3' UTR only stimulates translation in cis, without affecting the first round translation rate. These observations support a model in which the HCV 3' UTR retains ribosome complexes during translation termination to facilitate efficient initiation of subsequent rounds of translation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

siRNA carrying an (E)-vinylphosphonate moiety at the 5' end of the guide strand augments gene silencing by enhanced binding to human Argonaute-2

Efficient gene silencing by RNA interference (RNAi) in vivo requires the recognition and binding of the 5'- phosphate of the guide strand of an siRNA by the Argonaute protein. However, for exogenous siRNAs it is limited by the rapid removal of the 5'- phosphate of the guide strand by metabolic enzymes. Here, we have determined the crystal structure of human Argonaute-2 in complex with the metabolically stable 5'-(E)-vinylphosphonate (5'-E-VP) guide RNA at 2.5-Å resolution. The structure demonstrates how the 5' binding site in the Mid domain of human Argonaute-2 is able to adjust the key residues in the 5'-nucleotide binding pocket to compensate for the change introduced by the modified nucleotide. This observation also explains improved binding affinity of the 5'-E-VP -modified siRNA to human Argonaute-2 in-vitro, as well as the enhanced silencing in the context of the trivalent N-acetylgalactosamine (GalNAc)-conjugated siRNA in mice relative to the un-modified siRNA.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Targeted gene knock-in by homology-directed genome editing using Cas9 ribonucleoprotein and AAV donor delivery

Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide. However, combining RNPs with transgene-containing donor templates for targeted gene addition has proven challenging, which in turn has limited the capabilities of the RNP-mediated genome editing toolbox. Here, we demonstrate that combining RNP delivery with naturally recombinogenic adeno-associated virus (AAV) donor vectors enables site-specific gene insertion by homology directed genome editing. Compared to conventional plasmid-based expression vectors and donor templates, we show that combining RNP and AAV donor delivery increases the efficiency of gene addition by up to 12-fold, enabling the creation of lineage reporters that can be used to track the conversion of striatal neurons from human fibroblasts in real time. These results thus illustrate the potential for unifying nuclease protein delivery with AAV donor vectors for homology-directed genome editing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

A structural map of oncomiR-1 at single-nucleotide resolution

The miR-17–92a cluster, also known as ‘oncomiR-1’, is an RNA transcript that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. Its dysregulation underlies the development of several cancers. Oncomir-1 comprises six constituent miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. The structural mechanisms that regulate such differential processing are unknown, and this has impeded our understanding of the dysregulation of oncomiR-1 in pathophysiology. By probing the sensitivity of each nucleotide in oncomiR-1 to reactive small molecules, we present a secondary structural map of this RNA at single-nucleotide resolution. The secondary structure and solvent accessible regions of oncomiR-1 reveal that most of its primary microRNA domains are suboptimal substrates for Drosha-DGCR8, and therefore resistant to microprocessing. The structure indicates that the binding of trans-acting factors is required to remodel the tertiary organization and unmask cryptic primary microRNA domains to facilitate their processing into pre-microRNAs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Structural organization of a Type III-A CRISPR effector subcomplex determined by X-ray crystallography and cryo-EM

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated Cas proteins provide an immune-like response in many prokaryotes against extraneous nucleic acids. CRISPR–Cas systems are classified into different classes and types. Class 1 CRISPR–Cas systems form multi-protein effector complexes that includes a guide RNA (crRNA) used to identify the target for destruction. Here we present crystal structures of Staphylococcus epidermidis Type III-A CRISPR subunits Csm2 and Csm3 and a 5.2 Å resolution single-particle cryo-electron microscopy (cryo-EM) reconstruction of an in vivo assembled effector subcomplex including the crRNA. The structures help to clarify the quaternary architecture of Type III-A effector complexes, and provide details on crRNA binding, target RNA binding and cleavage, and intermolecular interactions essential for effector complex assembly. The structures allow a better understanding of the organization of Type III-A CRISPR effector complexes as well as highlighting the overall similarities and differences with other Class 1 effector complexes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Investigating the interaction between MED5 and CDK8 in Arabidopsis

Plant metabolic networks are precisely regulated by the spatial and temporal expression of suites of genes. Among the various transcription (co)factors, a multi‐protein complex, Mediator has been identified as a hub for transcription regulation. The core Mediator complex, comprising the head, middle and tail domains, functions as a bridge between transcription factors and basal transcription machinery, whereas the CDK8 kinase module plays a repressive regulatory role. It is still unclear, however, how the kinase module represses target genes especially in planta . Using a forward genetic screen, our lab determined that MED5, an Arabidopsis Mediator tail subunit, is required for maintaining phenylpropanoid homeostasis. A semi‐dominant mutant ( ref4‐3 ) characterized by a single amino acid substitution in MED5a (G383S) was isolated as a strong suppressor of phenylpropanoid pathway, indicated by decreased soluble phenylpropanoid metabolite accumulation, reduced lignin content and dwarfism. In contrast, knocking out MED5a and MED5b ( med5a/5b ) results in the accumulation of increased levels of phenylpropanoid pathway derivatives. Considering that the CDK8 kinase module is a repressive module in Mediator, we tested the hypothesis that Arabidopsis MED5 represses phenylpropanoid pathway by interacting with CDK8. To test this hypothesis, CDK8 knockout lines ( cdk8‐1 ) were crossed with ref4‐3 , and the phenylpropanoid content of the resulting double mutants was evaluated. In ref4‐3 cdk8‐1 plants, the concentration of sinapate esters and total lignin content are as low as they are in ref4‐3 , yet the growth defect in ref4‐3 is largely rescued. To further determine the genes targeted by MED5 and CDK8 in maintaining proper plant growth, we performed an RNA‐seq analysis which showed that a majority of the genes involved in salicylic acid (SA) biosynthesis and signaling are up‐regulated in ref4‐3 compared to wild type and ref4‐3 cdk8‐1 . Consistent with this observation, both free and total SA, both of which have been previously implicated in dwarfing in lignin‐modified plants, are accumulated to elevated levels in ref4‐3 but not in wild type and ref4‐3 cdk8‐1 . Nevertheless, blocking SA biosynthesis is not sufficient to restore the growth deficiency of ref4‐3 , suggesting that the hyperaccumulation of SA is more likely to be an effect rather than a cause for its dwarf phenotype. At the molecular level, to elucidate how ref4‐3 regulates downstream gene targets in either a CDK8‐dependent manner, we performed RNA polymerase II (Pol II) ChIP‐seq analysis in wild type, ref4‐3 , cdk8‐1 and ref4‐3 cdk8‐1 . The Pol II ChIP‐seq data may provide additional information for us to identify the genes that are causative for the dwarfism of ref4‐3 . Taken together, this study identifies the genetic interaction between MED5 and CDK8 in Arabidopsis, which enhances our understanding in the function of Mediator in plant metabolism and its role in lignin‐modification‐induced dwarfism. Support or Funding Information Department of Energy; Global Climate and Energy Project This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Mao, Xiangying↗
DOE OSTI2018

Moonshot Objectives: Catalyze New Scientific Breakthroughs—Proteogenomics

Breaking down the silos between disciplines to accelerate the pace of cancer research is a key paradigm for the Cancer Moonshot. Molecular analyses of cancer biology have tended to segregate between a focus on nucleic acids – DNA, RNA and their modifications – and a focus on proteins and protein function. Proteogenomics represents a fusion of those two fields, leveraging the strengths of each to provide a more integrated vision of the flow of information from DNA to RNA to protein and eventually function. Proteogenomic studies have been incorporated into multiple activities associated with the cancer moonshot, demonstrating substantial added value. Innovative study designs integrating genomic, transcriptomic and proteomic data, particularly those that use clinically relevant samples and engage clinical trials, are poised to provide new insights regarding cancer risk, progression, and response to therapy,

proteogenomics, proteomics, cancer moonshot, mass ↗