Proceedings. IEEE International Conference on Bioinformatics and Biomedicine最新文献

Graph theoretical measures have frequently been used to study disrupted connectivity in Alzheimer's disease human brain connectomes. However, prior studies have noted that differences in graph creation methods are confounding factors that may alter the topological observations found in these measures. In this study, we conduct a novel investigation regarding the effect of parcellation scale on graph theoretical measures computed for fiber density networks derived from diffusion tensor imaging. We computed 4 network-wide graph theoretical measures of average clustering coefficient, transitivity, characteristic path length, and global efficiency, and we tested whether these measures are able to consistently identify group differences among healthy control (HC), mild cognitive impairment (MCI), and AD groups in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort across 5 scales of the Lausanne parcellation. We found that the segregative measure of transtivity offered the greatest consistency across scales in distinguishing between healthy and diseased groups, while the other measures were impacted by the selection of scale to varying degrees. Global efficiency was the second most consistent measure that we tested, where the measure could distinguish between HC and MCI in all 5 scales and between HC and AD in 3 out of 5 scales. Characteristic path length was highly sensitive to the variation in scale, corroborating previous findings, and could not identify group differences in many of the scales. Average clustering coefficient was also greatly impacted by scale, as it consistently failed to identify group differences in the higher resolution parcellations. From these results, we conclude that many graph theoretical measures are sensitive to the selection of parcellation scale, and further development in methodology is needed to offer a more robust characterization of AD's relationship with disrupted connectivity.

Investigating the relationship between genetic variation and phenotypic traits is a key issue in quantitative genetics. Specifically for Alzheimer's disease, the association between genetic markers and quantitative traits remains vague while, once identified, will provide valuable guidance for the study and development of genetic-based treatment approaches. Currently, to analyze the association of two modalities, sparse canonical correlation analysis (SCCA) is commonly used to compute one sparse linear combination of the variable features for each modality, giving a pair of linear combination vectors in total that maximizes the cross-correlation between the analyzed modalities. One drawback of the plain SCCA model is that the existing findings and knowledge cannot be integrated into the model as priors to help extract interesting correlation as well as identify biologically meaningful genetic and phenotypic markers. To bridge this gap, we introduce preference matrix guided SCCA (PM-SCCA) that not only takes priors encoded as a preference matrix but also maintains computational simplicity. A simulation study and a real-data experiment are conducted to investigate the effectiveness of the model. Both experiments demonstrate that the proposed PM-SCCA model can capture not only genotype-phenotype correlation but also relevant features effectively.

Florida -the 3^rd most populous state in the USA-has the highest rates of Human Immunodeficiency Virus (HIV) infections and of unfavorable HIV outcomes, with marked social and racial disparities. In this work, we leveraged large-scale, real-world data, i.e., statewide surveillance records and publicly available data resources encoding social determinants of health (SDoH), to identify social and racial disparities contributing to individuals' risk of HIV infection. We used the Florida Department of Health's Syndromic Tracking and Reporting System (STARS) database (including 100,000+ individuals screened for HIV infection and their partners), and a novel algorithmic fairness assessment method -the Fairness-Aware Causal paThs decompoSition (FACTS)- merging causal inference and artificial intelligence. FACTS deconstructs disparities based on SDoH and individuals' characteristics, and can discover novel mechanisms of inequity, quantifying to what extent they could be reduced by interventions. We paired the deidentified demographic information (age, gender, drug use) of 44,350 individuals in STARS -with non-missing data on interview year, county of residence, and infection status- to eight SDoH, including access to healthcare facilities, % uninsured, median household income, and violent crime rate. Using an expert-reviewed causal graph, we found that the risk of HIV infection for African Americans was higher than for non- African Americans (both in terms of direct and total effect), although a null effect could not be ruled out. FACTS identified several paths leading to racial disparity in HIV risk, including multiple SDoH: education, income, violent crime, drinking, smoking, and rurality.

Hepatocellular carcinoma (HCC) has been an approved indication for the administration of immunotherapy since 2017, but biomarkers that predict therapeutic response have remained limited. Understanding and characterizing the tumor immune microenvironment enables better classification of these tumors and may reveal biomarkers that predict immunotherapeutic efficacy. In this paper, we applied a cell-type deconvolution algorithm using DNA methylation array data to investigate the composition of the tumor microenvironment in HCC. Using two publicly available datasets with a total cohort size of 57 patients, each with tumor and matched normal tissue samples, we identified key differences in immune cell composition. We found that NK cell abundance was significantly decreased in HCC tumors compared to adjacent normal tissue. We also applied DNA methylation "clocks" which estimate phenotypic aging and compared these findings to expression-based determinations of cellular senescence. Senescence and epigenetic aging was significantly increased in HCC tumors, and the degree of age acceleration and senescence was strongly associated with decreased NK cell abundance. In summary, we found that NK cell infiltration in the tumor microenvironment is significantly diminished, and that this loss of NK abundance is strongly associated with increased senescence and age-related phenotype. These findings point to key interactions between NK cells and the senescent tumor microenvironment and offer insights into the pathogenesis of HCC as well as potential biomarkers of therapeutic efficacy.

Alzheimer's disease (AD) is one of the most common and severe forms of Senile Dementia. Genome-wide association studies (GWAS) have identified dozens of AD susceptible loci. To better understand potential mechanism-of-action for AD, quantitative brain imaging features have been studied as mediators linking genetic variants to AD outcomes. In this study, Mediation analysis, Chow test and Mixed-effects Models are used to investigate the biological pathways by which genetic variants affect both brain structures/functions and disease diagnosis. We analyzed the imaging and genetics data collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project, including a Polygenic Hazard Score (PHS) and 13 imaging quantitative traits (QTs) extracted from the AV45 PET scans quantifying the amyloid deposition in different brain regions of subjects from four separate diagnostic groups. Mediation analysis assessed the mediating effects of image QTs between PHS and diagnosis, whereas Chow test and Linear Mixed-Effects models were used to characterize intra-group differences in the associations between genetic scores and imaging QTs for different disease stages. Results show that promising stage-specific imaging QTs that mediate the genetic effect of the studied PHS on disease status have been identified, providing novel insights into the predictive power of the PHS and the mediating power of amyloid imaging QTs with respect to multiple stages over the AD progression.

Subretinal injection (SI) is an ophthalmic surgical procedure that allows for the direct injection of therapeutic substances into the subretinal space to treat vitreoretinal disorders. Although this treatment has grown in popularity, various factors contribute to its difficulty. These include the retina's fragile, nonregenerative tissue, as well as hand tremor and poor visual depth perception. In this context, the usage of robotic devices may reduce hand tremors and facilitate gradual and controlled SI. For the robot to successfully move to the target area, it needs to understand the spatial relationship between the attached needle and the tissue. The development of optical coherence tomography (OCT) imaging has resulted in a substantial advancement in visualizing retinal structures at micron resolution. This paper introduces a novel foundation for an OCT-guided robotic steering framework that enables a surgeon to plan and select targets within the OCT volume. At the same time, the robot automatically executes the trajectories necessary to achieve the selected targets. Our contribution consists of a novel combination of existing methods, creating an intraoperative OCT-Robot registration pipeline. We combined straightforward affine transformation computations with robot kinematics and a deep neural network-determined tool-tip location in OCT. We evaluate our framework's capability in a cadaveric pig eye open-sky procedure and using an aluminum target board. Targeting the subretinal space of the pig eye produced encouraging results with a mean Euclidean error of 23.8μm.

Biomedical ontologies provide formalized information and knowledge in the biomedical domain. Over the years, biomedical ontologies have played an important role in facilitating biomedical research and applications. Common quality issues of biomedical ontologies include inconsistent naming of concepts, redundant concepts, redundant relations, incomplete/incorrect concept definitions, and incomplete/incorrect class hierarchies. In this work, we focus on addressing the incompleteness of the class hierarchy in SNOMED CT. We develop a substring replacement approach, leveraging concepts' lexical features and existing IS-A relations to identify potential missing IS-A relations in SNOMED CT. To evaluate the effectiveness of our approach, we performed both automated and manual validation. For the automated evaluation, we leverage relations from external terminologies in the Unified Medical Language System (UMLS) to validate the identified missing IS-A relations. For the manual validation, a randomly selected 100 samples from the results are reviewed by a domain expert. Applying our approach to the March 2022 release of SNOMED CT US Edition, we identified 3,228 potential missing IS-A relations, among which 63 were validated through the UMLS. The evaluation by the domain expert revealed that 89 out of 100 (a precision of 89%) missing IS-A relations are valid cases, showing the effectiveness of this substring replacement approach to facilitate the quality assurance of IS-A relations in SNOMED CT.

In proteomics, data-independent acquisition (DIA) has been shown to provide less biased and more reproducible results than data-dependent acquisition. Recently, many researchers have developed a series of methods to identify peptides and proteins by using spectrum libraries for DIA data. However, spectrum libraries are not always available for novel organisms or microbial communities. To detect peptides and proteins without a spectrum library, we developed IDIA, a library-free method using DIA data to generate pseudo-spectra that can be searched using conventional sequence database searching software. IDIA integrates two isotopic trace detection strategies and employs B-spline and Gaussian filters to help extract high-quality pseudo-spectra from the complex DIA data. The experimental results on human and yeast data demonstrated that our approach remarkably produced more peptide and protein identifications than the two state-of-the-art library-free methods, i.e., DIA-Umpire and Group-DIA. IDIA is freely available under the GNU GPL license at https://github.com/Biocomputing-Research-Group/IDIA.

The Orphanet Rare Disease Ontology (ORDO) provides a structured vocabulary encapsulating rare diseases. Downstream applications of ORDO depend on its accuracy to effectively perform their tasks. In this paper, we implement an automated quality assurance pipeline to identify missing is-a relations in ORDO. We first obtain lexical features from concept names. Then we generate related and unrelated feature sharing concept-pairs, where a feature sharing concept-pair can further generate derived term-pairs. If an unrelated and related feature sharing concept-pair generate the same derived term-pair, then we suggest a potential missing is-a relation between the unrelated feature sharing concept-pair. Applying this approach on the 2022-06-27 release of ORDO, we obtained 705 potential missing is-a relations. Leveraging external ontological information in the Unified Medical Language System, we validated 164 missing is-a relations. This indicates that our approach is a promising way to audit is-a relations in ORDO, even though further domain expert evaluation is still needed to validate the remaining potential missing is-a relations identified.

Goal: Identifying population differences can serve as an insightful tool for diagnostic radiology. To do so, a reliable preprocessing framework and data representation are vital.

Methods: We build a machine learning model to visualize gender differences in the circle of Willis (CoW), an integral part of the brain's vasculature. We start with a dataset of 570 individuals and process them for analysis using 389 for the final analysis.

Results: We find statistical differences between male and female patients in one image plane and visualize where they are. We can see differences between the right and left-hand sides of the brain confirmed using Support Vector Machines (SVM).

Conclusion: This process can be applied to detect population variations in the vasculature automatically.

Significance: It can guide debugging and inferring complex machine learning algorithms such as SVM and deep learning models.