Biology subjects

Javidi, A.

Publications and source records attributed to Javidi, A..

4 recordsLinked to original sources

bioRxiv2026

Benchmarking single-cell foundation models for real-world RNA-seq data integration

Single-cell foundation models enable reusable representations and streamlined analysis workflows, yet rigorous evaluation of their performance and robustness in real-world pharmaceutical settings remain underexplored. Here, we benchmarked leading single-cell foundation models (scGPT; scGPT_CP, a continually pretrained checkpoint of scGPT; scFoundation; scMulan; CellFM) against established baseline methods (scVI; Harmony) for data integration using over 1.5 million cells from clinical and preclinical samples. Performance was assessed using well-established and complementary metrics for technical correction and biological structure preservation. We further introduced robustness-oriented rankings to summarize metric trade-offs and quantify performance consistency across datasets and evaluation settings. Our findings show that fine-tuning improved technical correction performance; among the foundation models, fine-tuned scGPT_CP performed best. However, the baseline scVI was the top overall performer, ranking first by our multi-metric Leximax ranking and achieving the highest Pareto Front-1 hit. Collectively, our study provides practical insights for adapting foundation models to real-world drug design and development.

bioinformatics↗

bioRxiv2026

Benchmarking Next-Generation Sequencing Platforms: A Comprehensive Comparison Of Single-Cell RNA-Seq from Ultima UG 100 vs. Illumina NovaSeq X Plus

Single-cell RNA sequencing (scRNA-seq) has become an essential technology for dissecting cellular heterogeneity in complex biological systems, with Illumina platforms serving as the dominant NGS provider1-3. The recent emergence of the Ultima Genomics UG 100 platform offers a high-throughput and potentially more cost-effective alternative, warranting a rigorous comparative analysis. Here, we conducted a comprehensive head-to-head comparison of the Ultima Genomics UG 100 and Illumina NovaSeq X Plus platforms, generating deep-coverage scRNA-seq data from human PBMCs and stimulated T-cell samples. Our multi-level analysis revealed highly concordant performance in both cell type identification and gene expression. We found that both platforms robustly captured all major immune lineages and demonstrated good transcriptional agreement. Minor observed discrepancies were primarily correlated with low UMI counts, suggesting stochastic biological effects rather than technical variance. Overall, our study establishes that the Ultima UG 100 delivers performance highly comparable to the Illumina NovaSeq X Plus for single-cell transcriptomics.

bioinformatics↗

bioRxiv2022

Exploring the effect of mechanical anisotropy of protein structures in the unfoldase mechanism of AAA+ molecular machines

Essential cellular processes of microtubule disassembly and protein degradation, which span lengths from tens of m to nm, are mediated by specialized molecular machines with similar hexameric structure and function. Our molecular simulations at atomistic and coarse-grained scales show that both the microtubule severing protein spastin and the caseinolytic protease ClpY, accomplish spectacular unfolding of their diverse substrates, a microtubule lattice and dihydrofolate reductase (DHFR), by taking advantage of mechanical anisotropy in these proteins. By considering wild-type and variants of DHFR, we found that optimal ClpY-mediated action probes favorable orientations of the substrate relative to the machine. Unfolding of wild-type DHFR involves strong mechanical interfaces near each terminal and occurs along branched pathways, whereas unfolding of DHFR variants involves softer mechanical interfaces and occurs through single pathways, but translocation hindrance can arise from internal mechanical resistance. For spastin, optimum severing action initiated by pulling on a tubulin subunit is achieved through the orientation of the machine versus the substrate (microtubule lattice). Moreover, changes in the strength of the interactions between spastin and a microtubule filament, which can be driven by the tubulin code, lead to drastically different outcomes for the integrity of the hexameric structure of the machine.

biophysics↗

bioRxiv2021

Unfolding and Translocation of Knotted Proteins by Clp Biological Nanomachines: Synergistic Contribution of Primary Sequence and Topology Revealed by Molecular Dynamics Simulations

We use Langevin dynamics simulations to model, at atomistic resolution, how various natively-knotted proteins are unfolded in repeated allosteric translocating cycles of the ClpY ATPase. We consider proteins representative of different topologies, from the simplest knot (trefoil 31), to the three-twist 52 knot, to the most complex stevedore, 61, knot. We harness the atomistic detail of the simulations to address aspects that have so far remained largely unexplored, such as sequence-dependent effects on the ruggedness of the landscape traversed during knot sliding. Our simulations reveal the combined effect on translocation of the knotted protein structure, i.e. backbone topology and geometry, and primary sequence, i.e. side chain size and interactions, and show that the latter can even dominate translocation hindrance. In addition, we observe that, due to the interplay between the knotted topology and intramolecular contacts, the transmission of tension along the peptide chain occurs very differently from homopolymers. Finally, by considering native and non-native interactions, we examine how the disruption or formation of such contacts can affect the translocation processivity and concomitantly create multiple unfolding pathways with very different activation barriers.

biophysics↗