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Biology subjects

Vu, C.

Publications and source records attributed to Vu, C..

3 recordsLinked to original sources

An Ensemble Learning Approach to perform Link Prediction on Large Scale Biomedical Knowledge Graphs for Drug Repurposing and Discovery

Generating knowledge graph embeddings (KGEs) to represent entities (nodes) and relations (edges) in large scale knowledge graph datasets has been a challenging problem in representation learning. This is primarily because the embeddings / vector representations that are required to encode the full scope of data in a large heterogeneous graph needs to have a high dimensionality. The orientation of a large number of vectors requires a lot of space which is achieved by projecting the embeddings to higher dimensions. This is not a scalable solution especially when we expect the knowledge graph to grow in size in order to incorporate more data. Any efforts to constrain the embeddings to lower number of dimensions could be problematic as insufficient space to spatially orient the large number of embeddings / vector representations within limited number of dimensions could lead to poor inferencing on downstream tasks such as link prediction which leverage these embeddings to predict the likelihood of existence of a link between two or more entities in a knowledge graph. This is especially the case with large biomedical knowledge graphs which relate several diverse entities such as genes, diseases, signaling pathways, biological functions etc. that are clinically relevant for the application of KGs to drug discovery. The size of the biomedical knowledge graphs are therefore much larger compared to typical benchmark knowledge graph datasets. This poses a huge challenge in generating embeddings / vector representations of good quality to represent the latent semantic structure of the graph. Attempts to circumvent this challenge by increasing the dimensionality of the embeddings often render hardware limitations as generating high dimensional embeddings is computationally expensive and often times infeasible. To practically deal with representing the latent structure of such large scale knowledge graphs (KGs), our work proposes an ensemble learning model in which the full knowledge graph is sampled into several smaller subgraphs and KGE models generate embeddings for each individual subgraph. The results of link prediction from the KGE models trained on each subgraph are then aggregated to generate a consolidated set of link predictions across the full knowledge graph. The experimental results demonstrated significant improvement in rank-based evaluation metrics on task specific link predictions as well as general link predictions on four open-sourced biomedical knowledge graph datasets.

bioinformatics↗

RAPPID: a platform of ratiometric bioluminescent sensors for homogeneous immunoassays

Heterogeneous immunoassays such as ELISA have become indispensable in modern bioanalysis, yet translation into easy-to-use point-of-care assays is hindered by their dependence on external calibration and multiple washing and incubation steps. Here, we introduce RAPPID (Ratiometric Plug-and-Play Immunodiagnostics), a "mix-and-measure" homogeneous immunoassay platform that combines highly specific antibody-based detection with a ratiometric bioluminescent readout that can be detected using a basic digital camera. The concept entails analyte-induced complementation of split NanoLuc luciferase fragments, photoconjugated to an antibody sandwich pair via protein G adapters. We also introduce the use of a calibrator luciferase that provides a robust ratiometric signal, allowing direct in-sample calibration and quantitative measurements in complex media such as blood plasma. We developed RAPPID sensors that allow low-picomolar detection of several protein biomarkers, anti-drug antibodies, therapeutic antibodies, and both SARS-CoV-2 spike protein and anti-SARS-CoV-2 antibodies. RAPPID combines ratiometric bioluminescent detection with antibody-based target recognition into an easy-to-implement standardized workflow, and therefore represents an attractive, fast, and low-cost alternative to traditional immunoassays, both in an academic setting and in clinical laboratories for point-of-care applications.

bioengineering↗

Non-invasive brain perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: preliminary data

BackgroundThe paramagnetic properties of deoxyhemoglobin shorten T2* as do gadolinium based contrast agents. Induction of abrupt changes in arterial deoxyhemoglobin concentration ([dOHb]) can simulate intra-vascular injections of gadolinium for perfusion imaging. AimTo demonstrate the feasibility of making rapid changes in pulmonary venous hemoglobin saturation and employing the resulting changes in T2* to calculate flow metrics in the brain. MethodsA gas blender with a sequential gas delivery breathing circuit and software enabling prospective arterial blood gas targeting was used to implement rapid isocapnic lung changes in the partial pressure of blood oxygen (PaO2). Lung PO2 was initially lowered to induce a low baseline [dOHb]. PaO2 was then rapidly raised to PaO2 [~] 100 mmHg for 10 seconds and then rapidly returned to baseline. Blood oxygenation level dependent (BOLD) MRI signal changes were measured over time. ResultsArrival delay, signal amplitude and change in BOLD discriminated between large arteries, tissue and veins. The median half-time of BOLD signal in the middle cerebral artery was 1.7 s, indicating minimal dispersion confirming effective rapid modulation of pulmonary venous PO2. The contrast-to-noise ratio in the cortex was 3. Calculations of arrival delay, cerebral blood volume, mean transit time and cerebral blood flow were within normal ranges from published literature values. ConclusionNon-invasive induction of abrupt changes in [OHb] may function as a novel non-invasive vascular contrast agent for use in perfusion imaging.

neuroscience↗