Biology subjects

Arikan, M.

Publications and source records attributed to Arikan, M..

4 recordsLinked to original sources

bioRxiv2024

Microbiome signatures of virulence in the oral-gut-brain axis influence Parkinson's disease and cognitive decline pathophysiology

The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinsons Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals. Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with either mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of the gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells. Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.

microbiology↗

bioRxiv2023

OCT5k: A dataset of multi-disease and multi-graded annotations for retinal layers

The thickness and appearance of retinal layers are essential markers for diagnosing and studying eye diseases. Despite the increasing availability of imaging devices to scan and store large amounts of data, analyzing retinal images and generating trial endpoints has remained a manual, error-prone, and time-consuming task. In particular, the lack of large amounts of high-quality labels for different diseases hinders the development of automated algorithms. Therefore, we have compiled 5016 pixel-wise manual labels for 1672 optical coherence tomography (OCT) scans featuring two different diseases as well as healthy subjects to help democratize the process of developing novel automatic techniques. We also collected 4698 bounding box annotations for a subset of 566 scans across 9 classes of disease biomarker. Due to variations in retinal morphology, intensity range, and changes in contrast and brightness, designing segmentation and detection methods that can generalize to different disease types is challenging. While machine learning-based methods can overcome these challenges, high-quality expert annotations are necessary for training. Publicly available annotated image datasets typically contain few images and/or only cover a single type of disease, and most are only annotated by a single grader. To address this gap, we present a comprehensive multi-grader and multi-disease dataset fortraining machine learning-based algorithms. The proposed dataset covers three subsets of scans (Age-related Macular Degeneration, Diabetic Macular Edema, and healthy) and annotations for two types of tasks (semantic segmentation and object detection).

bioengineering↗

bioRxiv2023

Deep Active Learning for Robust Biomedical Segmentation

Deep learning for medical applications faces many unique challenges. A major challenge is the large amount of labelled data for training, while working in a relatively data scarce environment. Active learning can be used to overcome the vast data need challenge. A second challenged faced is poor performance outside of a experimental setting, contrary to the high requirement for safety and robustness. In this paper, we present a novel framework for estimating uncertainty metrics and incorporating a similarity measure to improve active learning strategies. To showcase effectiveness, a medical image segmentation task was used as an exemplar. In addition to faster learning, robustness was also addressed through adversarial perturbations. Using epistemic uncertainty and our framework, we can cut number of annotations needed by 39% and by 54% using epistemic uncertainty and a similarity metric.

bioengineering↗

bioRxiv2021

Stratification of the Gut Microbiota Composition Landscape Across the Alzheimer's Disease Continuum in a Turkish Cohort

Alzheimers disease (AD) is a heterogeneous neurodegenerative disorder that spans over a continuum with multiple phases including preclinical, mild cognitive impairment, and dementia. Unlike most other chronic diseases there are limited number of human studies reporting on AD gut microbiota in the literature. These published studies suggest that the gut microbiota of AD continuum patients varies considerably throughout the disease stages, raising expectations for existence of multiple microbiota community types. However, the community types of AD gut microbiota were not systematically investigated before, leaving important research gap for diet-based intervention studies and recently initiated precision nutrition approaches aiming at stratifying patients into distinct dietary subgroups. Here, we comprehensively assessed the community types of gut microbiota across the AD continuum. We analyze 16S rRNA amplicon sequencing of stool samples from 27 mild cognitive patients, 47 AD, and 51 non-demented control subjects using tools compatible with compositional nature of microbiota. To characterize gut microbiota community types, we applied multiple machine learning techniques including partitioning around the medoid clustering, fitting probabilistic Dirichlet mixture model, Latent Dirichlet Allocation model, and performed topological data analysis for population scale microbiome stratification based on Mapper algorithm. These four distinct techniques all converge on Prevotella and Bacteroides partitioning of the gut microbiota across AD continuum while some methods provided fine scale resolution in partitioning the community landscape. The Signature taxa and neuropsychometric parameters together robustly classify the heterogenous groups within the cohort. Our results provide a framework for precision nutrition approaches and diet-based intervention studies targeting AD cohorts. IMPORTANCEThe prevalence of AD worldwide is estimated to reach 131 million by 2050. Most disease modifying treatments and drug trials have failed due partly to the heterogeneous and complex nature of the disease. Unlike other neurodegenerative diseases gut microbiota of AD patients is poorly studied. Recently initiated ambitious precision nutrition initiative or other diet-based interventions can potentially be more effective if the heterogeneous disease such as AD is deconstructed into multiple strata allowing for better identification of biomarkers across narrower patient population for improved results. Because gut microbiota is inherently integral part of the nutritional interventions there is unmet need for microbiota-informed stratification of AD clinical cohorts in nutritional studies. Our study fills in this gap and draws attention to the need for microbiota stratification as one of the essential steps for precision nutrition interventions. We demonstrate that while Prevotella and Bacteroides clusters are the consensus partitions the newly developed probabilistic methods can provide fine scale resolution in partitioning the AD gut microbiome landscape.

microbiology↗