Biology subjects

Fallahzadeh, R.

Publications and source records attributed to Fallahzadeh, R..

3 recordsLinked to original sources

bioRxiv2021

Single-synapse analyses of Alzheimers disease implicate pathologic tau, DJ1, CD47, and ApoE

Synaptic molecular characterization is limited for Alzheimers disease (AD). We used mass cytometry to quantify 38 probes in approximately 17 million single synaptic events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), non-human primates (NHP), and PS/APP mice. Synaptic molecular integrity in humans and NHP was similar. Although not detected in human synapses, A{beta} was in PS/APP mice synaptic events. Clustering and pattern identification of human synapses showed expected disease-specific differences, like increased hippocampal pathologic tau in AD and reduced caudate dopamine transporter in LBD, and revealed novel findings including increased hippocampal CD47 and lowered DJ1 in AD and higher ApoE in AD dementia. Our results were independently supported by multiplex ion beam imaging of intact tissue.

neuroscience↗

bioRxiv2020

Integration of Mechanistic Immunological Knowledge into a Machine Learning Pipeline Increases Predictive Power

The dense network of interconnected cellular signaling responses quantifiable in peripheral immune cells provide a wealth of actionable immunological insights. While high-throughput single-cell profiling techniques, including polychromatic flow and mass cytometry, have matured to a point that enables detailed immune profiling of patients in numerous clinical settings, limited cohort size together with the high dimensionality of data increases the possibility of false positive discoveries and model overfitting. We introduce a machine learning platform, the immunological Elastic-Net (iEN), which incorporates immunological knowledge directly into the predictive models. Importantly, the algorithm maintains the exploratory nature of the high-dimensional dataset, allowing for the inclusion of immune features with strong predictive power even if not consistent with prior knowledge. In three independent studies our method demonstrates improved predictive power for clinically-relevant outcomes from mass cytometry data generated from whole blood, as well as a large simulated dataset.

bioinformatics↗

bioRxiv2019

Simulation-Based protein engineering of R. erythropolis NADH-FMN Oxidoreductase

The sulfur contents of fossil fuels has negative impacts on the environment and human health. The bio-catalytic desulfurization strategies and the biological refinement of the fossil fuels are a cost-effective process compared to chemical desulfurization. Rhodococcus erythropolis IGTS8 is able to extract the organic sulfur of oil as mineral salts by 4S metabolic pathway (i.e. DszA,B,C and D genes). dszD gene codes a NADH:FMN oxidoreductase delivering reducing equivalent to DszA, DszB, and DszC to remove sulfur from heterocyclic molecules. In this study, we sought to improve DszD specificity by side-direct mutagenesis based on prediction of the DszD structure, molecular docking, and molecular dynamic simulation. Accordingly, the cloning, expression and activity assay of best candidates (A79I and A79N) were performed. Our results demonstrated the important role of position 79 in enzyme activity, the A79I and A79N mutants are able to increase the enzyme activity 3.4 and 5.2 fold compared to wild-type.

bioinformatics↗