Biology subjects

Lotfi, M.

Publications and source records attributed to Lotfi, M..

3 recordsLinked to original sources

bioRxiv2026

MICA: Model-Informed Change-point Analysis

Change point detection is critical for identifying structural transitions in time series data. While most existing methods focus on changes in statistical properties of the data such as the mean or variance, many real-world systems are governed by dynamical models in which changes occur in model parameters. We introduce MICA, an algorithm that detects change points by minimizing the discrepancy between model simulations with a given dynamical model and observed data. The method integrates binary segmentation with a genetic algorithm to identify both the timing and nature of model parameter changes. MICA simultaneously estimates segment-specific and global parameters alongside change points, offering enhanced flexibility and interpretability. We demonstrate its utility on synthetic datasets and real-world scenarios, including COVID-19 epidemiological modeling, under policy interventions, and the analysis of generator cooling systems in wind turbines to monitor operational status. While illustrated using differential and difference equation models, MICA is model-agnostic and applicable to any simulatable system, making it broadly useful for applications requiring accurate tracking of structural dynamics.

systems biology↗

bioRxiv2025

plsMD: A plasmid reconstruction tool from short-read assemblies

While whole genome sequencing (WGS) has become a cornerstone of antimicrobial resistance (AMR) surveillance, the reconstruction of plasmid sequences from short-read WGS data remains a challenge due to repetitive sequences and assembly fragmentation. Current computational tools for plasmid identification and binning, such as PlasmidFinder, cBAR, PlasmidSPAdes, and Mob-recon, have limitations in reconstructing full plasmid sequences, hindering downstream analyses like phylogenetic studies and AMR gene tracking. To address this gap, we present plsMD, a tool designed for full plasmid reconstruction from short-read assemblies. plsMD integrates Unicycler assemblies with replicon and full plasmid sequence databases (PlasmidFinder, MOB-typer and PLSDB) to guide plasmid reconstruction through a series of contig manipulations. Using two datasets, one established benchmark dataset used in previous benchmarking studies and another novel dataset consisting of newly sequenced bacterial isolates, plsMD outperformed existing tools in both. In the benchmark dataset, it achieved excellent recall, precision, and F1 scores of 91.3%, 95.5%, and 92.0%, respectively. In the novel dataset, it achieved good recall, precision, and F1 scores of 77.6%, 88.9%, and 74.5%, respectively. plsMD supports two usage modalities: single-sample analysis for plasmid reconstruction and gene annotation, and batch-sample analysis for phylogenetic investigations of plasmid transmission. This computational tool represents a significant advancement in plasmid analysis, offering a robust solution for utilizing existing short-read WGS data to study plasmid-mediated AMR spread and evolution. Key pointsO_LIAccurate plasmid reconstruction from short-read assemblies, surpassing existing binning-based tools. C_LIO_LIReplicon-guided approach enables detection of divergent plasmids. C_LIO_LISupports single and batch sample analysis, enabling gene annotation as well as plasmid transmission and evolutionary studies. C_LI Bibliographical noteThe authors are members of the Genomics and Metagenomics Program at Childrens Cancer Hospital Egypt, working in cancer genomics, bioinformatics, and antimicrobial resistance research. Graphical abstractplsMD uses Unicycler assemblies to identify plasmid replicons via PlasmidFinder and MOB-typer, and aligns the assemblies to PLSDB. It refines alignments, selects reference plasmids, and reconstructs full plasmid sequences. Circular plasmids without replicons are identified separately. plsMD outputs plasmid and non-plasmid FASTA files. Two workflows are supported: single-sample (plasmid/non-plasmid separation, annotation of AMR, VF, IS, and replicons) and batch-sample (grouping plasmids by replicon, MAFFT alignment, rotation, and phylogenetic tree construction). Validation on two datasets showed notably better performance than other benchmarking tools. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/643493v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@719537org.highwire.dtl.DTLVardef@fb761dorg.highwire.dtl.DTLVardef@1076b72org.highwire.dtl.DTLVardef@1f2fd9_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2019

Crosstalk with the GAR-3 receptor contributes to feeding defects in Caenorhabditis elegans eat-2 mutants

Precise signaling at the neuromuscular junction (NMJ) is essential for proper muscle contraction. In the C. elegans pharynx, acetylcholine (ACh) released from the MC and M4 motor neurons stimulates two different types of contractions in adjacent muscle cells, termed pumping and isthmus peristalsis. MC stimulates rapid pumping through the nicotinic ACh receptor EAT-2, which is tightly localized at the MC NMJ, and eat-2 mutants exhibit a slow pump rate. Surprisingly, we found that eat-2 mutants also hyperstimulated peristaltic contractions, and these are characterized by increased and prolonged Ca2+ transients in the isthmus muscles. This hyperstimulation depends on crosstalk with the GAR-3 muscarinic acetylcholine receptor as gar-3 mutation specifically suppressed the prolonged contraction and increased Ca2+ observed in eat-2 mutant peristalses. Similar GAR-3 dependent hyperstimulation was also observed in mutants lacking the ace-3 acetylcholinesterase, and we suggest that NMJ defects in eat-2 and ace-3 mutants result in ACh stimulation of extrasynaptic GAR-3 receptors in isthmus muscles. gar-3 mutation also suppressed slow larval growth and prolonged lifespan phenotypes that result from dietary restriction in eat-2 mutants, indicating that crosstalk with the GAR-3 receptor has a long-term impact on feeding behavior and eat-2 mutant phenotypes. Article SummaryAcetylcholine stimulates different contractions in adjacent muscle cells in the C. elegans pharynx called pumping and peristalsis. The signaling mechanisms stimulating pumping have been characterized, but how these mechanisms affect peristalsis is unknown. Here we examined muscle contractions and Ca2+ transients during peristalsis in wild-type animals and acetylcholine signaling mutants. Surprisingly we found that while mutants affecting the eat-2 nicotinic acetylcholine receptor exhibited reduced pumping, they also hyperstimulated peristalses. This hyperstimulation depends on crosstalk with the GAR-3 muscarinic acetylcholine receptor in adjacent cells, and it contributes to the well-characterized dietary restriction and extended adult lifespan observed in eat-2 mutants.

neuroscience↗