We present Scaden, a deep neural network for cell deconvolution that uses gene expression information to infer the cellular composition of tissues. Scaden is trained on single-cell RNA sequencing (RNA-seq) data engineer discriminative features confer robustness bias and noise, making complex preprocessing feature selection unnecessary. demonstrate outperforms existing algorithms in both precision robustness. A single reliably deconvolves bulk RNA-seq microarray, human mouse tissue leverages...

A new CPMG-based multiple quantum relaxation dispersion experiment is presented for measuring millisecond dynamic processes at side-chain methyl positions in high molecular weight proteins. The benefits from a methyl-TROSY effect which cancellation of intramethyl dipole fields occurs, leading to 13C−1H correlation spectra sensitivity and resolution (Tugarinov, V.; Hwang, P. M.; Ollerenshaw, J. E.; Kay, L. E. Am. Chem. Soc. 2003, 125, 10420−10428). utility the methodology illustrated with an...

Allosteric regulation is an effective mechanism of control in biological processes. In allosteric proteins a signal originating at one site the molecule communicated through protein structure to trigger specific response remote site. Using NMR relaxation dispersion techniques we directly observe dynamic process which KIX domain CREB binding communicates information between sites. mediates cooperativity pairs transcription factors two distinct interaction surfaces manner. We show that...

The hexameric Escherichia coli RNA chaperone Hfq (Hfq(Ec)) is involved in riboregulation of target mRNAs by small trans-encoded RNAs. proteins different bacteria comprise an evolutionarily conserved core, whereas the C-terminus variable length. Although structure core has been elucidated for several proteins, no structural information yet obtained C-terminus. Using bioinformatics, nuclear magnetic resonance spectroscopy, synchrotron radiation circular dichroism (SRCD) spectroscopy and angle...

New relaxation dispersion experiments are presented that probe millisecond time-scale dynamical processes in proteins. The measure the of 1H−15N multiple-quantum coherence as a function rate application either 1H or 15N refocusing pulses during constant time interval. In contrast to profiles generated from more conventional 15N(1H) single-quantum depend on changes chemical shifts between exchanging states, dispersions sensitive environments both and spins. resulting can, therefore, be quite...

Marked for life. For the characterization of larger proteins new NMR spectroscopy methods that focus on side-chain methyl groups have been developed by using selectively isotope-labeled precursor compounds. Here we report synthesis a 13C-methyl-group-labeled methionine preparative scale, and its incorporation into SH2 domain protein PLC-γ1 (see scheme).

The refolding kinetics of bistable RNA sequences were studied in unperturbed equilibrium via 13C exchange NMR spectroscopy. For this purpose a straightforward labeling technique was elaborated using 2′-13C-methoxy uridine modification, which prepared by two-step synthesis and introduced into standard protocols. Using longitudinal spectroscopy the 20 nt characterized at temperatures between 298 310 K, yielding enthalpy entropy differences conformers activation energy process. more stable 32...

Numerous recent insights into the complex and dynamic cellular signatures of biological function, development disease are owed to technical advances in single-cell transcriptome profiling. The deep understanding biology that single cell expression experiments can deliver comes at a cost, as complexity size data poses unique challenges computational analysis algorithmic development. In this review, we highlight machine learning allow for efficient integration data, identification known novel...

In this work, we present a novel 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radical phosphoramidite building block, which can be attached to the 5′-terminus of nucleic acids. To investigate paramagnetic relaxation enhancement (PRE) emanating from center, incorporated TEMPO label into various types RNAs. We measured proton PREs for selectively 13C-isotope labeled nucleotides derive long-range distance restraints in short 15 nucleotide stem–loop model system, underscoring potential 5′-TEMPO...

NMR relaxation dispersion techniques were used to investigate conformational exchange of the three-helix bundle protein KIX under native conditions. These experiments provide site-resolved kinetic information about microsecond-to-millisecond time scale motions along with structural (chemical shift) without requiring a perturbation equilibrium. All data are consistent an apparent two-state transition between natively folded and partially unfolded high-energy state that is populated 3.0 ± 0.2%...

Longitudinal exchange experiments facilitate the quantification of rates interconversion between exchanging species, along with their longitudinal relaxation rates, by analyzing time-dependence direct correlation and cross peaks. Here we present a simple robust alternative to this strategy, which is based on combination two complementary experiments, one without resolving We show that combining data sets systematic errors are caused differential line-broadening species avoided reliable...

A novel spectral entropy interpretation for protein NOESY data is presented the investigation of spatial distribution residues in structures without requirement NOE cross peak assignments. In this approach individual traces Si(ω) from a 3D 15N NOESY-HSQC taken at frequency positions corresponding to different amide groups (residue position i) are subjected self-convolution procedure thus leading autocorrelation function Ci(ω) NOESY-trace particular backbone residue position. The...

Abstract We present Scaden, a deep neural network for cell deconvolution that uses gene expression information to infer the cellular composition of tissues. Scaden is trained on single RNA-seq data engineer discriminative features confer robustness bias and noise, making complex preprocessing feature selection unnecessary. demonstrate outperforms existing algorithms in both precision robustness. A reliably deconvolves bulk microarray, human mouse tissue leverages combined multiple sets. Due...

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPeptide Plane Torsion Angles in Proteins through Intraresidue 1H−15N−13C‘ Dipole−CSA Relaxation Interference: Facile Discrimination between Type-I and Type-II β-TurnsKarin Kloiber Robert KonratView Author Information Institute of Organic Chemistry University Innsbruck, Austria Cite this: J. Am. Chem. Soc. 2000, 122, 48, 12033–12034Publication Date (Web):November 15, 2000Publication History Received27 June 2000Revised9 October 2000Published...

A novel NMR method is demonstrated for the investigation of protein ligand interactions. In this approach an adiabatic fast passage pulse, i.e. a long, weak pulse with linear frequency sweep, used to probe 1H−1H NOEs. During effective rotating-frame NOE weighted average transverse and longitudinal cross-relaxation contributions that can be tuned by power sweep rate. It occurrence spin diffusion processes leads sizable deviations from theoretical relationship between relaxation rate tilt...

Although originally designed for broadband inversion and decoupling in NMR spectroscopy, recent methodological developments have introduced adiabatic fast passage (AFP) pulses into the field of protein dynamics. AFP employ a frequency sweep, not only superior properties with respect to offset effects, but they are also easily implemented pulse sequence. As magnetization is dragged from +z −z direction, Larmor precession impeded since becomes spin-locked, which potentially useful feature...

Switching of DNA: We address the conformational heterogeneity DNA on secondary structure level. While it has been demonstrated that RNA is able to modulate function by changing its folding state, we show for first time too can undergo transitions between energetically similar states a scale relevant biological processes (see figure). Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made...

The solution structure of quail CRP2(LIM2) was significantly improved by using an increased number NOE constraints obtained from a 13C,15N-labeled protein sample and applying recently developed triple-resonance cross-correlated relaxation experiment for the determination backbone dihedral angle ψ. Additionally, relative orientation 15N(i)−1HN(i) dipole 13CO(i) CSA tensor, which is related to both angles φ ψ, probed nitrogen−carbonyl multiple-quantum used as additional constraint refinement...

Abstract Background Recent technological advances have resulted in an unprecedented increase publicly available biomedical data, yet the reuse of data is often precluded by experimental bias and a lack annotation depth consistency. Missing annotations makes it impossible for researchers to find datasets specific their needs. Findings Here, we investigate RNA-sequencing metadata prediction based on gene expression values. We present deep-learning–based domain adaptation algorithm automatic...