Performance tuning non-uniform sampling for sensitivity enhancement of signal-limited biological NMR

Palmer, Melissa R.; Wenrich, Broc R.; Stahlfeld, Phillip; Rovnyak, David

doi:10.1007/s10858-014-9823-5

Cited by 41 publications

(61 citation statements)

References 25 publications

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“…For further experimental confirmation, recently reported data 32 also provide an example of how NUS i SNR enhancements are governed by Eqs. 7ab, included here in the supporting information (Figure S2).…”

Section: Theoretical Resultsmentioning

confidence: 72%

“…32 Once the receiver is turned off, the i SNR is fixed. Although spectra can be produced with apparent SNR greater than the i SNR, the apparent SNR is constrained by the original signal.…”

Section: Theoretical Resultsmentioning

confidence: 99%

“…T 2 / T SMP ≥2), does not yield the same resolution as uniform sampling over the same evolution time and the increase in signal resolution with evolution time by biased NUS is complex and needs more investigation. 7,8,32 …”

Section: Theoretical Resultsmentioning

confidence: 99%

“…32 The i SNR of this sinusoid will be analyzed by equations 2, and 4. The sampling density prior to normalizing its area versus uniform sampling is…”

Section: Theoretical Resultsmentioning

confidence: 99%

“…Indeed, it is useful from this point on to distinguish the signal-to-noise ratio of the raw data prior to post-acquisition manipulations as the intrinsic SNR, or i SNR. 32 Any improvement in the i SNR of the acquired time domain data is then available to subsequent spectral reconstruction techniques, regardless of whether they are linear or not. Since a variety of computational techniques can be used to increase the apparent SNR starting from the i SNR, we recognize that the i SNR is a fundamental constraint on detecting a peak, and thus a peak is intrinsically more detectable if its i SNR is improved.…”

Section: Introductionmentioning

confidence: 99%

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Sensitivity of Nonuniform Sampling NMR

et al. 2015

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Many information rich multi-dimensional experiments in nuclear magnetic resonance spectroscopy can benefit from a signal-to-noise ratio (SNR) enhancement up to about two-fold if a decaying signal in an indirect dimension is sampled with nonconsecutive increments, termed non-uniform sampling (NUS). This work provides formal theoretical results and applications to resolve major questions on the scope of the NUS enhancement. First, we introduce the NUS Sensitivity Theorem, that any decreasing sampling density applied to any exponentially decaying signal always results in higher sensitivity (SNR per square root of measurement time) than uniform sampling (US). Several cases will illustrate this theorem, and show that even conservative applications of NUS improve sensitivity by useful amounts. Next, we turn to a serious limitation of uniform sampling: the SNR by US decreases for extending evolution times, and thus total experimental times, beyond 1.26 T2 (T2 = signal decay constant). Thus SNR and resolution cannot be simultaneously improved by extending US beyond 1.26 T2. We find that NUS can eliminate this constraint, and introduce the Matched NUS SNR Theorem: an exponential sampling density matched to the signal decay always improves the SNR with additional evolution time. Though proved for a specific case, broader classes of NUS densities also improve SNR with evolution time. Applications of these theoretical results are given for a soluble plant natural product and a solid tripeptide (u-13C,15N-MLF). These formal results clearly demonstrate the inadequacies of applying US to decaying signals in indirect nD-NMR dimensions, supporting broader adoption of NUS.

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Section: Theoretical Resultsmentioning

confidence: 72%

“…32 Once the receiver is turned off, the i SNR is fixed. Although spectra can be produced with apparent SNR greater than the i SNR, the apparent SNR is constrained by the original signal.…”

Section: Theoretical Resultsmentioning

confidence: 99%

Section: Theoretical Resultsmentioning

confidence: 99%

“…32 The i SNR of this sinusoid will be analyzed by equations 2, and 4. The sampling density prior to normalizing its area versus uniform sampling is…”

Section: Theoretical Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sensitivity of Nonuniform Sampling NMR

et al. 2015

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A Set of Efficient nD NMR Protocols for Resonance Assignments of Intrinsically Disordered Proteins

et al. 2016

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The RF pulse scheme RN[N-CA HEHAHA]NH, which provides a convenient approach to the acquisition of different multidimensional chemical shift correlation NMR spectra leading to backbone resonance assignments, including those of the proline residues of intrinsically disordered proteins (IDPs), is experimentally demonstrated. Depending on the type of correlation data required, the method involves the generation of in-phase ((15) N)(x) magnetisation via different magnetisation transfer pathways such as H→N→CO→N, HA→CA→CO→N, H→N→CA→N and H→CA→N, the subsequent application of (15) N-(13) C(α) heteronuclear Hartmann-Hahn mixing over a period of ≈100 ms, chemical-shift labelling of relevant nuclei before and after the heteronuclear mixing step and amide proton detection in the acquisition dimension. It makes use of the favourable relaxation properties of IDPs and the presence of (1) JCαN and (2) JCαN couplings to achieve efficient correlation of the backbone resonances of each amino acid residue "i" with the backbone amide resonances of residues "i-1" and "i+1". It can be implemented in a straightforward way through simple modifications of the RF pulse schemes commonly employed in protein NMR studies. The efficacy of the approach is demonstrated using a uniformly ((15) N,(13) C) labelled sample of α-synuclein. The different possibilities for obtaining the amino-acid-type information, simultaneously with the connectivity data between the backbone resonances of sequentially neighbouring residues, have also been outlined.

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Resolution‐enhanced 2D NMR of complex mixtures by non‐uniform sampling

Guennec

Dumez

Giraudeau

et al. 2015

Magnetic Reson in Chemistry

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NMR is a powerful tool for the analysis of complex mixtures and the identification of individual components. Two-dimensional (2D) NMR potentially offers a wealth of information, but resolution is often sacrificed in order to contain experimental times. We explore the use of non-uniform sampling (NUS) to increase substantially the resolution of 2D NMR spectra of complex mixtures of small molecules, with no increase in experimental time. Two common pulse sequences for metabolomics applications are analysed, HSQC and TOCSY. Specific attention is paid to sensitivity in resolution-enhanced NUS spectra, using the signal-to-maximum-noise ratio as a metric. With a careful choice of sampling schedule and reconstruction algorithm, resolution in the (13) C dimension for HSQC is increased by a factor of at least 32, with no loss in sensitivity and no spurious peaks. For TOCSY, multiplets can be resolved in the indirect dimension in a reasonable experimental time. These properties should increase the usefulness of 2D NMR for metabolomics applications by, for example, increasing the chances of metabolite identification.

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Performance tuning non-uniform sampling for sensitivity enhancement of signal-limited biological NMR

Cited by 41 publications

References 25 publications

Sensitivity of Nonuniform Sampling NMR

Sensitivity of Nonuniform Sampling NMR

A Set of Efficient nD NMR Protocols for Resonance Assignments of Intrinsically Disordered Proteins

Resolution‐enhanced 2D NMR of complex mixtures by non‐uniform sampling

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