Biology subjects

Lieberman, J. A.

Publications and source records attributed to Lieberman, J. A..

3 recordsLinked to original sources

bioRxiv2021

Magnetic Resonance Spectroscopy Frequency and Phase Correction Using Convolutional Neural Networks

We introduce DeepSPEC, a novel convolutional neural network (CNN) -based approach for frequency-and-phase correction (FPC) of MRS spectra to achieve fast and accurate FPC of single-voxel PRESS MRS and MEGA-PRESS data. In DeepSPEC, two neural networks, including one for frequency correction and one for phase correction were trained and validated using published simulated and in vivo PRESS and MEGA-PRESS MRS dataset with wide-range artificial frequency and phase offsets applied. DeepSPEC was subsequently tested and compared to the current deep learning solution - a "vanilla" neural network approach using multilayer perceptrons (MLP). Furthermore, random noise was added to the original simulated dataset to further investigate the model performance with noise at varied signal-to-noise (SNR) levels (i.e., 6 dB, 3 dB, and 1.5 dB). The testing showed that DeepSPEC is more robust to noise compared to the MLP-based approach due to having a smaller absolute error in both frequency and phase offset prediction. The DeepSPEC framework was capable of correcting frequency offset with 0.01{+/-}0.01 Hz and phase offset with 0.12{+/-}0.09{degrees} absolute errors on average for unseen simulated data at a high SNR (12 dB) and correcting frequency offset with 0.01{+/-}0.02 Hz and phase offset within -0.07{+/-}0.44{degrees} absolute errors on average at very low SNR (1.5 dB). Furthermore, additional frequency and phase offsets (i.e., small, moderate, large) were applied to the in vivo dataset, and DeepSPEC demonstrated better performance for FPC when compared to the MLP-based approach. Results also show DeepSPEC has superior performance than the model-based SR implementation (mSR) in FPC by having higher accuracy in a wider range of additional offsets. These results represent a proof of concept for the use of CNNs for preprocessing MRS data and demonstrate that DeepSPEC accurately predicts frequency and phase offsets at varying noise levels with state-of-the-art performance.

neuroscience↗

bioRxiv2021

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3-6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

immunology↗

bioRxiv2020

Control of RNA polymerase II promoter-proximal pausing by DNA supercoiling

The accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) complexes, and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered general positive facilitators of transcription. Here we show that, in contrast to this general assumption, human topoisomerase IIa accumulates at gene promoters, where it removes transcription-associated negative DNA supercoiling and represses transcription by enforcing promoter-proximal pausing of Pol II. We demonstrate that this topological balance is essential to maintain Immediate Early Genes under basal repression conditions, and that its disruption creates a positive feedback loop that explains their typical bursting behavior in response to stimulus. We therefore describe the control of promoter DNA supercoiling by topoisomerases as a novel layer for the regulation of gene expression, which can act as a molecular switch to rapidly activate transcription.

molecular biology↗