Abstract:
:Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48-72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Satpathy S,Jaehnig EJ,Krug K,Kim BJ,Saltzman AB,Chan DW,Holloway KR,Anurag M,Huang C,Singh P,Gao A,Namai N,Dou Y,Wen B,Vasaikar SV,Mutch D,Watson MA,Ma C,Ademuyiwa FO,Rimawi MF,Schiff R,Hoog J,Jacobs S,Malovdoi
10.1038/s41467-020-14381-2subject
Has Abstractpub_date
2020-01-27 00:00:00pages
532issue
1issn
2041-1723pii
10.1038/s41467-020-14381-2journal_volume
11pub_type
杂志文章abstract::Compounds with incommensurate structural modulations have been extensively studied in last several decades. However, the relationship between structurally incommensurate/commensurate phases and associated electronic states remains enigmatic. Here we report the coexisting of complex incommensurate structures and highly...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6358
更新日期:2014-11-07 00:00:00
abstract::R-loops are stable nucleic acid structures that have important physiological functions, but which also pose a significant threat to genomic stability. Increased R-loops cause replication stress and chromosome fragility and have been associated with diseases such as neurodegeneration and cancer. Although excessive R-lo...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-06677-1
更新日期:2018-10-19 00:00:00
abstract::It has previously been postulated that the Earth's hydrous mantle transition zone may play a key role in intraplate magmatism, but no confirmatory evidence has been reported. Here we demonstrate that hydrothermally altered subducted oceanic crust was involved in generating the late Cenozoic Chifeng continental flood b...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8700
更新日期:2015-07-14 00:00:00
abstract::Rapid and accurate clinical diagnosis remains challenging. A component of diagnosis tool development is the design of effective classification models with Mass spectrometry (MS) data. Some Machine Learning approaches have been investigated but these models require time-consuming preprocessing steps to remove artifacts...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19354-z
更新日期:2020-11-05 00:00:00
abstract::Gene-targeted animal models that are generated by injecting Cas9 and sgRNAs into zygotes are often accompanied by undesired double-strand break (DSB)-induced byproducts and random biallelic targeting due to uncontrollable Cas9 targeting activity. Here, we establish a parental allele-specific gene-targeting (Past-CRISP...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18391-y
更新日期:2020-09-14 00:00:00
abstract::Dark matter-only simulations of galaxy formation predict many more subhalos around a Milky Way-like galaxy than the number of observed satellites. Proposed solutions require the satellites to inhabit dark matter halos with masses 10(9)-10(10 )Msun at the time they fell into the Milky Way. Here we use a modelling appro...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8599
更新日期:2015-07-02 00:00:00
abstract::It is well known that high-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and E7 was identified as one of the key initiators in HPV-mediated carcinogenesis. Here we show that lactate dehydrogenase A (LDHA) preferably locates in the nucleus in HPV16-positive cervical tumors du...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-06841-7
更新日期:2018-10-24 00:00:00
abstract::The occurrence of Oceanic Anoxic Event 2 (OAE2) 94 million years ago is considered to be one of the largest carbon cycle perturbations in the Earth's history. The marked increase in the spatial extent of the anoxic conditions in the world's oceans associated with OAE2 resulted in the mass accumulation of organic-rich ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1233
更新日期:2011-01-01 00:00:00
abstract::Alkaline-urea aqueous solvent system provides a novel and important approach for the utilization of polysaccharide. As one of the most important polysaccharide, chitosan can be well dissolved in this solvent system, and the resultant hydrogel material possesses unique and excellent properties. Thus the sound understan...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12033
更新日期:2016-06-23 00:00:00
abstract::O-GlcNAcylation has been implicated in the tumorigenesis of various tissue origins, but its function in liver tumorigenesis is not clear. Here, we demonstrate that O-GlcNAcylation can enhance the expression, stability and function of Yes-associated protein (YAP), the downstream transcriptional regulator of the Hippo p...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15280
更新日期:2017-05-05 00:00:00
abstract::Past studies of the end-Permian extinction (EPE), the largest biotic crisis of the Phanerozoic, have not resolved the timing of events in southern high-latitudes. Here we use palynology coupled with high-precision CA-ID-TIMS dating of euhedral zircons from continental sequences of the Sydney Basin, Australia, to show ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07934-z
更新日期:2019-01-23 00:00:00
abstract::In magnetic materials, the Pauli exclusion principle typically drives anti-alignment between electron spins on neighbouring species resulting in antiferromagnetic behaviour. Ferromagnetism exhibiting spontaneous spin alignment is a fairly rare behaviour, but once materialized is often associated with itinerant electro...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7677
更新日期:2015-03-25 00:00:00
abstract::Cortical neurons are often functionally heterogeneous even for molecularly defined subtypes. In sensory cortices, physiological responses to natural stimuli can be sparse and vary widely even for neighboring neurons. It is thus difficult to parse out circuits that encode specific stimuli for further experimentation. H...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03183-2
更新日期:2018-02-28 00:00:00
abstract::While engineering the phase and structure of electrocatalysts could regulate the performance of many typical electrochemical processes, its importance to the carbon dioxide electroreduction has been largely unexplored. Herein, a series of phase and structure engineered copper-tin dioxide catalysts have been created an...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07419-z
更新日期:2018-11-22 00:00:00
abstract::The inheritance of the centrosome during human fertilization remains mysterious. Here we show that the sperm centrosome contains, in addition to the known typical barrel-shaped centriole (the proximal centriole, PC), a surrounding matrix (pericentriolar material, PCM), and an atypical centriole (distal centriole, DC) ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04678-8
更新日期:2018-06-07 00:00:00
abstract::Layered materials embrace rich intercalation reactions to accommodate high concentrations of foreign species within their structures, and find many applications spanning from energy storage, ion exchange to secondary batteries. Light alkali metals are generally most easily intercalated due to their light mass, high ch...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13809
更新日期:2016-12-14 00:00:00
abstract::Planar neural networks and interfaces serve as versatile in vitro models of central nervous system physiology, but adaptations of related methods to three dimensions (3D) have met with limited success. Here, we demonstrate for the first time volumetric functional imaging in a bioengineered neural tissue growing in a t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4997
更新日期:2014-06-05 00:00:00
abstract::The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function and proliferation. Here we show that the pancreatic beta-cells in zebrafish exhibit different growth-promoting and functional properties, ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00461-3
更新日期:2017-09-22 00:00:00
abstract::The Mesoamerican and Caribbean (MAC) region is characterized by tropical cyclones (TCs), strong El Niño-Southern Oscillation events, and climate variability that bring unique hazards to socio-ecological systems. Here we report the first characterization of the isotopic evolution of a TC (Hurricane Otto, 2016) in the M...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12062-3
更新日期:2019-09-20 00:00:00
abstract::Many heritable mutualisms, in which beneficial symbionts are transmitted vertically between host generations, originate as antagonisms with parasite dispersal constrained by the host. Only after the parasite gains control over its transmission is the symbiosis expected to transition from antagonism to mutualism. Here,...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02052-8
更新日期:2017-11-29 00:00:00
abstract::Subglacial lakes are widespread beneath the Antarctic Ice Sheet but their control on ice-sheet dynamics and their ability to harbour life remain poorly characterized. Here we present evidence for a palaeo-subglacial lake on the Antarctic continental shelf. A distinct sediment facies recovered from a bedrock basin in P...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15591
更新日期:2017-06-01 00:00:00
abstract::Purkinje cells (PCs) in Crus 1 represent whisker movement via linear changes in firing rate, but the circuit mechanisms underlying this coding scheme are unknown. Here we examine the role of upstream inputs to PCs-excitatory granule cells (GCs) and inhibitory molecular layer interneurons-in processing of whisking sign...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00312-1
更新日期:2017-08-10 00:00:00
abstract::Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca(2+)-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we d...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8947
更新日期:2015-08-06 00:00:00
abstract::In November 2013, a series of earthquakes began along a mapped ancient fault system near Azle, Texas. Here we assess whether it is plausible that human activity caused these earthquakes. Analysis of both lake and groundwater variations near Azle shows that no significant stress changes were associated with the shallow...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7728
更新日期:2015-04-21 00:00:00
abstract::Bell correlations are a foundational demonstration of how quantum entanglement contradicts the classical notion of local realism. Rigorous validation of quantum nonlocality have only been achieved between solid-state electron spins, internal states of trapped atoms, and photon polarisations, all weakly coupling to gra...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12192-8
更新日期:2019-10-01 00:00:00
abstract::Monitoring the Earth's stress state plays a role in our understanding of an earthquake's mechanism and in the distribution of hazards. Crustal deformation due to the July 2019 earthquake sequence in Ridgecrest (California) that culminated in a preceding quake of magnitude (M) 6.4 and a subsequent M7.1 quake caused str...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16867-5
更新日期:2020-06-17 00:00:00
abstract::ATP-dependent chromatin remodellers are mutated in more than 20% of human cancers. The consequences of these mutations on enzyme function are poorly understood. Here, we characterise the effects of CHD4 mutations identified in endometrial carcinoma on the remodelling properties of dMi-2, the highly conserved Drosophil...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04503-2
更新日期:2018-05-29 00:00:00
abstract::Acoustic sensors play an important role in many areas, such as homeland security, navigation, communication, health care and industry. However, the fundamental pressure detection limit hinders the performance of current acoustic sensing technologies. Here, through analytical, numerical and experimental studies, we sho...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6247
更新日期:2014-10-15 00:00:00
abstract::Because of the potential impact on agriculture and other key human activities, efforts have been dedicated to the local control of precipitation. The most common approach consists of dispersing small particles of dry ice, silver iodide, or other salts in the atmosphere. Here we show, using field experiments conducted ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1462
更新日期:2011-08-30 00:00:00
abstract::A number of modes of oscillations of particles and fields can exist in space plasmas. Since the early 1970s, space missions have observed noise-like plasma waves near the geomagnetic equator known as 'equatorial noise'. Several theories were suggested, but clear observational evidence supported by realistic modelling ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8703
更新日期:2015-07-14 00:00:00