Biology subjects

Lyu, T.

Publications and source records attributed to Lyu, T..

4 recordsLinked to original sources

bioRxiv2026

A Framework for SPICE MRSI Reconstruction Posterior Uncertainty Quantification

Purpose: Low-rank reconstruction methods such as SPICE substantially improve Magnetic Resonance Spectroscopic Imaging (MRSI) reconstruction quality. However, SPICE does not provide an estimate of reconstruction uncertainty. A framework for posterior uncertainty estimation in SPICE reconstruction is proposed, hereafter referred to as the framework. Theory and Methods: A Laplace approximation is used to estimate the covariance of the reconstructed spatial coefficients. This covariance is propagated through the spectral basis and spectral fitting to obtain metabolite concentration uncertainty. Matrix-free Hessian--vector products and voxel-wise conjugate-gradient estimation are used to avoid explicit construction or inversion of the full Hessian, making the method tractable. Results: Validation using repeated in vivo 7 T MRSI acquisitions showed that the estimated posterior uncertainty exhibited spatial and spectral patterns similar to those of empirical repeated-scan uncertainty. Experiments further demonstrated how spatial regularization and k-space undersampling affect the estimated uncertainty. Conclusion: The framework provides a practical framework for uncertainty quantification when using SPICE reconstruction of MRSI. It could be adapted to other regularised low-rank reconstruction methods.

neuroscience↗

bioRxiv2024

Mechanism of D-type cyclins recognition by the AMBRA1 E3 ligase receptor

AMBRA1 is a tumour suppressor protein that functions as a substrate receptor in the ubiquitin conjugation system and regulates the stability of D-type cyclins and cell proliferation. Here, we present the cryo-EM structure of cyclin D1 bound AMBRA1-DDB1 complex at 3.5 [A] resolution. The structure reveals a substrate interaction surface on the AMBRA1 WD40 domain that specifically binds to the C-terminal region of D-type cyclins. This interaction is dependent on the phosphorylation of Thr286 residue in the C-terminal phosphodegron site of D-type cyclins. The phosphodegron motif folds into a turn-like conformation followed by a 310 helix that promotes its assembly with AMBRA1. Additionally, we show that AMBRA1 mutants, which are defective in cyclin D1 binding, lead to cyclin D1 accumulation and DNA damage. Understanding the AMBRA1-D-type cyclins structure enhances the knowledge of the molecular mechanisms that govern the cell cycle control and may lead to new therapeutic approaches for cancers linked to abnormal cyclin D activity.

biochemistry↗

bioRxiv2019

An optimized 16S rRNA sequencing protocol for vaginal microbiome to avoid biased abundance estimation

We applied three 16S rRNA sequencing protocols on vaginal microbiome samples, to evaluate whether they produce unbiased estimation of vaginal microbiome composition. We modified the 27F primer (hereafter denoted as 27F). Using vaginal samples from 28 healthy women and 10 women with bacterial vaginosis, we sequenced three 16S rRNA sequencing protocols, i.e., 27F-338R, 27F-338R and 341F-806R protocols, naming after their PCR primer sets, to test whether the sequencing results are consistent with the clinical diagnostics, morphology and qPCR results. First, the 27F primer would not align with Gardnerlla vaginalis very well, leading to poor amplification of such species. By modifying the primer sequences, the modified 27F primer (27F) was able to amplify Gardnerlla vaginalis very well. Second, the DNA sequence of characteristic species Lactobacillus crispatus is identical with Lactobacillus garrinarum, leading to biased estimation of abundance of Lactobacillus crispatus when using V3-V4 as PCR target region; in contrast, such bias did not occur when using V1-V2 as a target region. Third, optimized 27F-338R avoided above-mentioned biases and restored the well-established community state types (CSTs) clustering. ImportanceVaginal microbiome has profound effects on the health of women and their newborns. Our study found that two well-established 16S rDNA sequencing protocols led to systementical biased estimation of characteristic species of vaginal microbiome. Subsequent analysis proved that the PCR primer fetching efficacy and target region identity were major contributor for such bias. With carefully selected target region and optimized PCR primer set, we were able to eliminate such biases and provide accurate estimation of vaginal microbiome, which showed high consistency with clinical diagnostics. We modified the 27F primer (27F). Using the optimized PCR primer set of 27F and 338R to target the V1-V2 hyper-variable region, our 16S rRNA sequencing correctly evaluate the composition of vaginal microbiome.

microbiology↗

bioRxiv2019

Structural basis for the binding selectivity of human CDY chromodomains

The CDY (Chromodomain on the Y) family is a small family of chromodomain containing proteins, whose chromodomains closely resemble those in HP1 and Polycomb. The CDY proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. Based on our structural, binding and mutagenesis data, we synthesized a more CDYL1/2 selective peptidic ligand UNC4850. Our work provides critical implications that CDYL1bs role in the regulation of neural development is dependent on its recognition of lysine-methylated ARKS motifs.

molecular biology↗