Biology subjects

Ozdemir, I.

Publications and source records attributed to Ozdemir, I..

3 recordsLinked to original sources

bioRxiv2025

Transgenerational maintenance of H3K27me3 heterochromatin is balanced by chromodomain proteins in Caenorhabditis elegans

The ability to replicate and pass information to descendants is a fundamental requirement for life. In addition to the DNA-based genetic information, modifications of the DNA or DNA-associated proteins can create patterns of heritable gene regulation. Such epigenetic inheritance allows for adaptation without mutation, but its limits and regulation are incompletely understood. Here we developed a C. elegans system to study the transgenerational epigenetic inheritance of H3K27me3, a conserved histone posttranslational modification associated with gene repression. We find that induced alterations of the genome-wide H3K27me3 landscape and the associated fertility defects persist for many generations in genetically wildtype descendants under selective pressure. We uncover that the inheritance of the altered H3K27me3 landscape is regulated by two chromodomain proteins with antagonizing functions, and provide mechanistic insight into how this molecular memory is initiated and maintained. Our results demonstrate that epigenetic inheritance can act as a mutation-independent, heritable mechanism of adaptation. In BriefOzdemir et al. demonstrate that an altered genomic distribution of the histone modification H3K27me3 can be epigenetically inherited across many generations through the activity of HERI-1/SET-32/MES-4, which is antagonized by CEC-6/PRC2 in C. elegans. HighlightsO_LIAltered H3K27me3 landscapes can be inherited for at least 15 generations in C. elegans. C_LIO_LIThe chromodomain proteins CEC-6 and HERI-1 have opposite roles in antagonizing or promoting the maintenance of the altered H3K27me3 landscape. C_LIO_LIH3K23me3 and H3K36me3 replace H3K27me3 to promote the intergenerational and transgenerational inheritance of the altered epigenome. C_LI

genetics↗

bioRxiv2023

The AGNOSTIC MRS Benchmark Dataset: Deep Learning for Out-of-voxel Artifacts

Neural networks are potentially valuable for many of the challenges associated with MRS data. The purpose of this manuscript is to describe the AGNOSTIC dataset, which contains 259,200 synthetic 1H MRS examples for training and testing neural networks. AGNOSTIC was created using 270 basis sets that were simulated across 18 field strengths and 15 echo times. The synthetic examples were produced to resemble in vivo brain data with combinations of metabolite, macromolecule, residual water signals, and noise. To demonstrate the utility, we apply AGNOSTIC to train two Convolutional Neural Networks (CNNs) to address out-of-voxel (OOV) echoes. A Detection Network was trained to identify the point-wise presence of OOV echoes, providing proof of concept for real-time detection. A Prediction Network was trained to reconstruct OOV echoes, allowing subtraction during post-processing. Complex OOV signals were mixed into 85% of synthetic examples to train two separate CNNs for the detection and prediction of OOV signals. AGNOSTIC is available through Dryad and all Python 3 code is available through GitHub. The Detection network was shown to perform well, identifying 95% of OOV echoes. Traditional modeling of these detected OOV signals was evaluated and may prove to be an effective method during linear-combination modeling. The Prediction Network greatly reduces OOV echoes within FIDs and achieved a median log10 normed-MSE of -1.79, an improvement of almost two orders of magnitude.

neuroscience↗

bioRxiv2023

Downfield Proton MRSI with whole-brain coverage at 3T

PurposeTo develop a 3D downfield magnetic resonance spectroscopic imaging (DF-MRSI) protocol with whole brain coverage and post-processing pipeline for creation of metabolite maps. MethodsA 3D, circularly phase-encoded version of the previously developed 2D DF-MRSI sequence with [Formula] spectral-spatial excitation and frequency selective refocusing was implemented and tested in 5 healthy volunteers at 3T. Downfield metabolite maps with a nominal spatial resolution of 0.7 cm3 were recorded in 8 slices at 3T in a scan time of 22m 40s. An MRSI post-processing pipeline was developed to create DF metabolite maps. Metabolite concentrations and uncertainty estimates were compared between region differences for nine downfield peaks. ResultsLCModel analysis showed CRLB average values of 3-4% for protein amide resonances in the three selected regions (anterior cingulate (ACC), dorsolateral prefrontal cortex (DLPFC), and centrum semiovale (CSO)); CRLBs were somewhat higher for individual peaks but for the most part were less than 20%. While DF concentration maps were visually quite homogeneous throughout the brain, general linear regression analysis corrected for multiple comparisons found significant differences between CSO and DLPFC for peaks at 7.09 ppm (p= 0.014), 7.90 ppm (p=0.009), 8.18 ppm (p=0.009), combined amides (p=0.009), and between ACC and DLPFC for the 7.30 ppm peak (p=0.020). CRLB values were not significantly different between brain regions for any of the DF peaks. Conclusion3D DF-MRSI of the human brain at 3T with wide spatial coverage for the mapping of exchangeable amide and other resonances is feasible at a nominal spatial resolution of 0.7 cm3.

bioengineering↗