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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.

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At least 1,171 records · Page 65
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Functionalized mesoporous silica nanoparticles for oral delivery of budesonide

Non-functionalized and amino-functionalized mesoporous silica nanoparticle were loaded with anti-inflammatory drug budesonide and additionally post-coated with bioadhesive polymer (carbopol). TEM images showed spherical shape of the nanoparticles and slightly higher polydispersity after coating with carbopol. Nitrogen physisorption and thermogravimetic analysis revealed that more efficient loading and incorporation into the pores of nanoparticles was achieved with the amino-functionalized silica carrier. Infrared spectra indicated that the post-coating of these nanoparticles with carbopol led to the formation of bond between amino groups of the functionalized carrier and carboxyl groups of carbopol. The combination of amino-functionalization of the carrier with the post-coating of the nanoparticles sustained budesonide release. Further, an in vitro model of inflammatory bowel disease showed that the cytoprotective effect of budesonide loaded in the post-coated silica nanoparticles on damaged HT-29 cells was more pronounced compared to the cytoprotection obtained with pure budesonide. -- Graphical abstract: Silica mesoporous MCM-41 particles were amino-functionalized, loaded with budesonide and post-coated with bioadhesive polymer (carbopol) in order to achieve prolonged residence of anti-inflammatory drug in GIT. Highlights: • Higher drug loading in amino-functionalized mesoporous silica. • Amino-functionalization and post-coating of the nanoparticles sustained drug release. • Achievement of higher cytoprotective effect with drug loaded into the nanoparticles.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

A color-tunable luminescent material with functionalized graphitic carbon nitride as multifunctional supports

A color-tunable luminescent material was prepared based on the composition of functionalized graphitic carbon nitride (g-C{sub 3}N{sub 4}) and europium (III). The functionalized g-C{sub 3}N{sub 4} layers not only behave as multifunctional supports including ligand coordinated with europium (III) and a support structure for the formation of the luminescent material, but exhibit excitation wavelength-dependent luminescence, thus the energy transfer between the functionalized g-C{sub 3}N{sub 4} and europium (III) can match very well by controlling the emission wavelength of functionalized g-C{sub 3}N{sub 4}. The as-prepared materials was comprehensively characterized via X-ray photoelectron spectroscopy, Fourier Transform Infrared spectroscopy, X-ray scattering techniques, Ultraviolet and Visible spectrophotometer, fluorescence spectrophotometer, thermogravimetric analysis, etc. The luminescent material exhibits multi-color emissions which are consistent with the characteristic emissions of europium (III) and functionalized g-C{sub 3}N{sub 4}, and the photoluminescence quality and density of the europium (III) can be greatly enhanced. The brilliant optical properties of the materials make them suiting for multipurpose applications in practical fields. - Graphical abstract: Schematic illustration of the synthesis and basic composition of the luminescent material. Inset figures were luminescence emission spectra of g-C{sub 3}N{sub 4} (A), europium (III) complex (a) and luminescent material (b) with the same concentration in (B) (K{sub ex}=350 nm) and photographs of (left) H{sub 2}O and (right) the H{sub 2}O dispersion of luminescence emission spectra under 350 nm UV radiation. The energy transfer in the luminescent material matchs very well and it exhibits multi-color emissions simultaneously. The enhanced photoluminescence quality and density of the europium (III) makes them suiting for multipurpose applications in practical fields. - Highlights: • Luminescent material exhibits multi-color emissions when excited by single wavelength. • The energy trsnsfer between functionalized g-C{sub 3}N{sub 4} and europium matches very vell. • Functionalized g-C{sub 3}N{sub 4} exhibits excitation wavelength-depengdent bright blue luminescence. • Functionalized g-C{sub 3}N{sub 4} layer provided as multifunctional supports.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

Effect of α{sub 7} nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

How Accurate Are the Minnesota Density Functionals for Noncovalent Interactions, Isomerization Energies, Thermochemistry, and Barrier Heights Involving Molecules Composed of Main-Group Elements?

The 14 Minnesota density functionals published between the years 2005 and early 2016 are benchmarked on a comprehensive database of 4986 data points (84 data sets) involving molecules composed of main-group elements. The database includes noncovalent interactions, isomerization energies, thermochemistry, and barrier heights, as well as equilibrium bond lengths and equilibrium binding energies of noncovalent dimers. Additionally, the sensitivity of the Minnesota density functionals to the choice of basis set and integration grid is explored for both noncovalent interactions and thermochemistry. By and large, the main strength of the hybrid Minnesota density functionals is that the best ones provide very good performance for thermochemistry (e.g., M06-2X), barrier heights (e.g., M08-HX, M08-SO, MN15), and systems heavily characterized by self-interaction error (e.g., M06-2X, M08-HX, M08-SO, MN15), while the main weakness is that none of them are state-of-the-art for the full spectrum of noncovalent interactions and isomerization energies (although M06-2X is recommended from the 10 hybrid Minnesota functionals). Similarly, the main strength of the local Minnesota density functionals is that the best ones provide very good performance for thermochemistry (e.g., MN15-L), barrier heights (e.g., MN12-L), and systems heavily characterized by self-interaction error (e.g., MN12-L and MN15-L), while the main weakness is that none of them are state-of-the-art for the full spectrum of noncovalent interactions and isomerization energies (although M06-L is clearly the best from the four local Minnesota functionals). Finally, as an overall guide, M06-2X and MN15 are perhaps the most broadly useful hybrid Minnesota functionals, while M06-L and MN15-L are perhaps the most broadly useful local Minnesota functionals, although each has different strengths and weaknesses.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

How Well Can the M06 Suite of Functionals Describe the Electron Densities of Ne, Ne 6+ , and Ne 8+ ?

The development of better approximations to the exact exchange-correlation functional is essential to the accuracy of density functionals. A recent study indicated that functionals with few parameters offer more accurate electron densities than recently developed many-parameter functionals for light closed-shell atomic systems. In this study, we calculated electron densities, their gradients, and Laplacians of Ne, Ne 6+ , and Ne 8+ using 19 electronic structure methods, and we compared them to the CCSD reference results. Two basis sets, namely, aug-cc-pωCV5Z and aug-cc-pV5Z, are utilized in the calculations. We found that the choice of basis set has a significant impact on the errors and rankings of some of the selected methods. The errors of electron densities, their gradients, and Laplacians calculated with the aug-cc-pV5Z basis set are substantially reduced, especially for Minnesota density functionals, as compared to the results using the aug-cc-pωCV5Z basis set (a larger basis set utilized in earlier work (Medvedev et al. Science2017, 355, 49–52)). The rankings of the M06 suite of functionals among the 19 methods are greatly improved with the aug-cc-pV5Z basis set. Furthermore, the performances of the HSE06, BMK, MN12-L, and MN12-SX functionals are also improved with the aug-cc-pV5Z basis set. The M06 suite of functionals is capable of providing accurate electron densities, gradients, and Laplacians using the aug-cc-pV5Z basis set, and thus it is suitable for a wide range of applications in chemistry and physics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Improving Predictions of Spin-Crossover Complex Properties through DFT Calculations with a Local Hybrid Functional

We conducted a study on the performance of the local hybrid exchange-correlation functional PBE0r for a set of 95 experimentally-characterized iron spin crossover (SCO) complexes. The PBE0r functional is a variant of PBE0 where the exchange correction is restricted to on-site terms formulated within the basis of local orbitals. We determine the free parameters of the PBE0r functional against experimental data and other hybrid functionals. With a Hartree-Fock (HF) exchange factor of 4%, the PBE0r functional accurately reproduces the electronic and free energy trends predicted in prior DFT studies for these 95 complexes using the B3LYP functional. Larger values of HF exchange stabilize high-spin states. The PBE0r-predicted bond lengths tend to exceed the experimental bond lengths, and bond lengths are less sensitive to HF exchange. The predicted SCO transition temperatures T 1/2 from PBE0r correlate moderately with the experimental transition temperatures, showing a slight improvement compared to the previous modB3LYP-predicted T 1/2 . Furthermore, this study suggests the PBE0r functional as computationally cost-effective and offers the possibility of simulating larger complexes with accuracy comparable to other global hybrid functionals, provided the HF exchange parameter is carefully optimized.

25 ENERGY STORAGE↗
DOE OSTI2017

Intrinsic Resolution of Molecular Electronic Wave Functions and Energies in Terms of Quasi-atoms and Their Interactions

A general intrinsic energy resolution has been formulated for strongly correlated wave functions in the full molecular valence space and its subspaces. The information regarding the quasi-atomic organization of the molecular electronic structure is extracted from the molecular wave function without introducing any additional postulated model state wave functions. To this end, the molecular wave function is expressed in terms of quasi-atomic molecular orbitals, which maximize the overlap between subspaces of the molecular orbital space and the free-atom orbital spaces. As a result, the molecular wave function becomes the superposition of a wave function representing the non-bonded juxtaposed quasi-atoms and a wave function describing the interatomic electron migrations that create bonds through electron sharing. The juxtaposed nonbonded quasi-atoms are shown to consist of entangled quasi-atomic states from different atoms. The binding energy is resolved as a sum of contributions that are due to quasi-atom formation, quasiclassical electrostatic interactions and interatomic interferences caused by electron sharing. The contributions are further resolved according to orbital interactions. The various transformations that generate the analysis are determined by criteria that are independent of the working orbital basis used for calculating the molecular wave function. Lastly, the theoretical formulation of the resolution is quantitatively validated by an application to the C 2 molecule.

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

Work Function Engineering of 2D Materials: The Role of Polar Edge Reconstructions

2D materials have attracted tremendous interest as functional materials because of their diverse and tunable properties, especially at their edges. A material’s work function is a critical parameter in many electronic devices; however, a fundamental understanding and a path toward large alterations of the work function in 2D materials still remain elusive. Here in this paper, we report the first evidence for anisotropy of the work function in 2D MoS 2 from first-principles calculations. We also demonstrate large work-function tunability (in the range of 3.45–6.29 eV) choosing the 2H phase of MoS 2 as a model system by sampling various edge configurations. We furthermore reveal the origin of this work function anisotropy and tunability by extending the existing work function relation to the local dipole moment at surfaces of 3D materials to those at edges in 2D materials. We then use machine-learning approaches to correlate work function with edge structures. These results pave the way for intrinsic edge engineering for electronic and catalytic applications.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Mountain biodiversity and ecosystem functions: interplay between geology and contemporary environments

Although biodiversity and ecosystem functions are strongly shaped by contemporary environments, such as climate and local biotic and abiotic attributes, relatively little is known about how they depend on long-term geological processes. Here, along a 3000-m elevational gradient with tectonic faults on the Tibetan Plateau (that is, Galongla Mountain in Medog County, China), we study the joint effects of geological and contemporary environments on biological communities, such as the diversity and community composition of plants and soil bacteria, and ecosystem functions. We find that these biological communities and ecosystem functions generally show consistent elevational breakpoints at 2000–2800 m, which coincide with Indus-Yalu suture zone fault and are similar to the elevational breakpoints of soil bacteria on another mountain range 1000 km away. Mean annual temperature, soil pH and moisture are the primary contemporary determinants of biodiversity and ecosystem functions, which support previous findings. However, compared with the models excluding geological processes, inclusion of geological effects, such as parent rock and weathering, increases 67.9 and 35.9% of the explained variations in plant and bacterial communities, respectively. Such inclusion increases 27.6% of the explained variations in ecosystem functions. The geological processes thus provide additional links to ecosystem properties, which are prominent but show divergent effects on biodiversity and ecosystem functions: parent rock and weathering exert considerable direct effects on biodiversity, whereas indirectly influence ecosystem functions via interactions with biodiversity and contemporary environments. Thus, the integration of geological processes with environmental gradients could enhance our understanding of biodiversity and, ultimately, ecosystem functioning across different climatic zones.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Control of work functions of nanophotonic components

Work function is an essential material’s property playing important roles in electronics, photovoltaics, and more recently, in nanophotonics. We have studied effects of organic, and inorganic dielectric materials on work functions of Au films in single layered, and multilayered structures. We found that measured work function of metallic surfaces can be affected by dielectric materials situated 10–100 nm away from the metallic surface. We have found that, (i) the glass underneath ~ 50 nm gold slab reduces the work function of gold, (ii) Rh590:PMMA increases the work function of a gold film deposited on top of the polymer, and (iii) reduces it if Rh590:PMMA is deposited on top of Au. (iv) With increase of the Rh590 concentration in PMMA, n, the work function first decreases (at n < 64 g/l), and then increases (at n > 64 g/l). (v) The work function of a Fabry–Perot cavity or an MIM waveguide is almost the same as that of single Au films of comparable thickness. The experimental results can be qualitatively explained in terms of a simple model taking into account adhesion of charged molecules to a metallic surface, and formation of a double layer of charges accelerating or decelerating electrons exiting the metal and decreasing or increasing the work function.

36 MATERIALS SCIENCE↗
DOE OSTI2014

Towards improved local hybrid functionals by calibration of exchange-energy densities

A new approach for the calibration of (semi-)local and exact exchange-energy densities in the context of local hybrid functionals is reported. The calibration functions are derived from only the electron density and its spatial derivatives, avoiding spatial derivatives of the exact-exchange energy density or other computationally unfavorable contributions. The calibration functions fulfill the seven more important out of nine known exact constraints. It is shown that calibration improves substantially the definition of a non-dynamical correlation energy term for generalized gradient approximation (GGA)-based local hybrids. Moreover, gauge artifacts in the potential-energy curves of noble-gas dimers may be corrected by calibration. The developed calibration functions are then evaluated for a large range of energy-related properties (atomization energies, reaction barriers, ionization potentials, electron affinities, and total atomic energies) of three sets of local hybrids, using a simple one-parameter local-mixing. The functionals are based on (a) local spin-density approximation (LSDA) or (b) Perdew-Burke-Ernzerhof (PBE) exchange and correlation, and on (c) Becke-88 (B88) exchange and Lee-Yang-Parr (LYP) correlation. While the uncalibrated GGA-based functionals usually provide very poor thermochemical data, calibration allows a dramatic improvement, accompanied by only a small deterioration of reaction barriers. In particular, an optimized BLYP-based local-hybrid functional has been found that is a substantial improvement over the underlying global hybrids, as well as over previously reported LSDA-based local hybrids. It is expected that the present calibration approach will pave the way towards new generations of more accurate hyper-GGA functionals based on a local mixing of exchange-energy densities.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Action-angle formulation of generalized, orbit-based, fast-ion diagnostic weight functions

Due to the usually complicated and anisotropic nature of the fast-ion distribution function, diagnostic velocity-space weight functions, which indicate the sensitivity of a diagnostic to different fast-ion velocities, are used to facilitate the analysis of experimental data. Additionally, when velocity-space weight functions are discretized, a linear equation relating the fast-ion density and the expected diagnostic signal is formed. In a technique known as velocity-space tomography, many measurements can be combined to create an ill-conditioned system of linear equations that can be solved using various computational methods. However, when velocity-space weight functions (which by definition ignore spatial dependencies) are used, velocity-space tomography is restricted, both by the accuracy of its forward model and also by the availability of spatially overlapping diagnostic measurements. In this work, we extend velocity-space weight functions to a full 6D generalized coordinate system and then show how to reduce them to a 3D orbit-space without loss of generality using an action-angle formulation. Moreover, we show how diagnostic orbit-weight functions can be used to infer the full fast-ion distribution function, i.e., orbit tomography. In depth derivations of orbit weight functions for the neutron, neutral particle analyzer, and fast-ion D-α diagnostics are also shown

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2018

Predicting vapor liquid equilibria using density functional theory: A case study of argon

Predicting vapor liquid equilibria (VLE) of molecules governed by weak van der Waals (vdW) interactions using the first principles approach is a significant challenge. Due to the poor scaling of the post Hartree-Fock wave function theory with system size/basis functions, the Kohn-Sham density functional theory (DFT) is preferred for systems with a large number of molecules. However, traditional DFT cannot adequately account for medium to long range correlations which are necessary for modeling vdW interactions. Recent developments in DFT such as dispersion corrected models and nonlocal van der Waals functionals have attempted to address this weakness with a varying degree of success. In this work, we predict the VLE of argon and assess the performance of several density functionals and the second order Møller-Plesset perturbation theory (MP2) by determining critical and structural properties via first principles Monte Carlo simulations. PBE-D3, BLYP-D3, and rVV10 functionals were used to compute vapor liquid coexistence curves, while PBE0-D3, M06-2X-D3, and MP2 were used for computing liquid density at a single state point. Here, the performance of the PBE-D3 functional for VLE is superior to other functionals (BLYP-D3 and rVV10). At T = 85 K and P = 1 bar, MP2 performs well for the density and structural features of the first solvation shell in the liquid phase.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Predicting the thermodynamic stability of double-perovskite halides from density functional theory

Recently, a series of double-perovskite halide compounds such as Cs 2 AgBiCl 6 and Cs 2 AgBiBr 6 have attracted intensive interest as promising alternatives to the solar absorber material CH 3 NH 3 PbI 3 because they are Pb-free and may exhibit enhanced stability. The thermodynamic stability of a number of double-perovskite halides has been predicted based on density functional theory (DFT) calculations of compound formation energies. In this paper, we found that the stability prediction can be dependent on the approximations used for the exchange-correlation functionals, e.g., the DFT calculations using the widely used Perdew, Burke, Ernzerhof (PBE) functional predict that Cs 2 AgBiBr 6 is thermodynamically unstable against phase-separation into the competing phases such as AgBr, Cs 2 AgBr 3 , Cs 3 Bi 2 Br 9 , etc., obviously inconsistent with the good stability observed experimentally. The incorrect prediction by the PBE calculation results from its failure to predict the correct ground-state structures of AgBr, AgCl, and CsCl. By contrast, the DFT calculations based on local density approximation, optB86b-vdW, and optB88-vdW functionals predict the ground-state structures of these binary halides correctly. Furthermore, the optB88-vdW functional is found to give the most accurate description of the lattice constants of the double-perovskite halides and their competing phases. Given these two aspects, we suggest that the optB88-vdW functional should be used for predicting thermodynamic stability in the future high-throughput computational material design or the construction of the Materials Genome database for new double-perovskite halides. As a result, using different exchange-correlation functionals has little influence on the dispersion of the conduction and the valence bands near the electronic bandgap; however, the calculated bandgap can be affected indirectly by the optimized lattice constant, which varies for different functionals.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Rotational memory function of SPC/E water

Memory effects are essential for the dynamics of condensed materials and are responsible for non-exponential relaxation of correlation functions of dynamic variables through the memory function. Memory functions of dipole rotations for water have never been calculated directly from molecular dynamics simulations. We present here calculations of memory functions for single-dipole rotations and for the overall dipole moment of the sample for SPC/E water. The normalized memory functions for single-particle and collective dipole dynamics turn out to be nearly identical. This result validates theories of dielectric spectroscopy in terms of single-particle time correlation functions and the connection between the collective and single-particle relaxation times through the Kirkwood factor. The dielectric function in this formalism contains no new dynamic information that does not exist in the single-dipole correlation function. A short memory time, ≲1 fs, justifies the use of the mathematics of rotational diffusion to describe the dynamics of a single molecular dipole moment in bulk water. Here, an analytical equation for the rotational memory time is derived.

Asthagiri, Dilipkumar N. [Oak Ridge National Labor↗
DOE OSTI2024

Codiscovering graphical structure and functional relationships within data: A Gaussian Process framework for connecting the dots

Most problems within and beyond the scientific domain can be framed into one of the following three levels of complexity of function approximation. Type 1: Approximate an unknown function given input/output data. Type 2: Consider a collection of variables and functions, some of which are unknown, indexed by the nodes and hyperedges of a hypergraph (a generalized graph where edges can connect more than two vertices). Given partial observations of the variables of the hypergraph (satisfying the functional dependencies imposed by its structure), approximate all the unobserved variables and unknown functions. Type 3: Expanding on Type 2, if the hypergraph structure itself is unknown, use partial observations of the variables of the hypergraph to discover its structure and approximate its unknown functions. These hypergraphs offer a natural platform for organizing, communicating, and processing computational knowledge. While most scientific problems can be framed as the data-driven discovery of unknown functions in a computational hypergraph whose structure is known (Type 2), many require the data-driven discovery of the structure (connectivity) of the hypergraph itself (Type 3). We introduce an interpretable Gaussian Process (GP) framework for such (Type 3) problems that does not require randomization of the data, access to or control over its sampling, or sparsity of the unknown functions in a known or learned basis. Its polynomial complexity, which contrasts sharply with the super-exponential complexity of causal inference methods, is enabled by the nonlinear ANOVA capabilities of GPs used as a sensing mechanism.

Science & Technology - Other Topics↗
DOE OSTI2016

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies. Molecular & Cellular Proteomics 16: 10.1074/mcp.M116.060301, 121–134, 2017.

59 BASIC BIOLOGICAL SCIENCES↗