Biology subjects

Salehi-Ashtiani, K.

Publications and source records attributed to Salehi-Ashtiani, K..

10 recordsLinked to original sources

bioRxiv2026

Coupling of oceanographic state to the dark proteome: a foundation for genome-informed marine productivity modeling

Phytoplankton drive ~46% of global primary production, yet whether their protein repertoires encode ocean conditions - and whether reference databases capture the environmentally responsive fraction - is unknown. We used a protein language model to classify 447.7 million proteins from 2,357 samples and analyzed domain profiles for 231.7 million algal proteins across 2,044 samples. Under spatial block cross-validation, environment predicted individual domain abundances at R2 up to 0.59, while domain profiles predicted sea surface temperature at R2 = 0.38. The strongest coupling lay beyond annotated sequence space: 33,950 families clustered from 201 million Pfam-dark proteins coupled to environment 2.29-fold more strongly than Pfam domains. Cross-taxonomic selection, protein language modeling, and AlphaFold 3 predictions of 138 well-folded, InterPro-unannotated representatives support the Pfam-dark proteome as a biologically structured evolutionary compartment. Thus, the proteins most tightly coupled to ocean state are those least represented in reference databases.

bioinformatics↗

bioRxiv2026

Conserved metabolic vulnerabilities across pathogenic coronaviruses nominate host-directed therapeutic targets

Pathogenic coronaviruses profoundly rewire host cell metabolism to support viral replication, yet whether these metabolic alterations expose shared and actionable vulnerabilities remains unclear. By integrating transcriptomic profiles from cells infected with SARS-CoV, SARS-CoV-2, and MERS-CoV with genome-scale metabolic models, we identify conserved and virus-specific metabolic perturbations affecting mitochondrial transport, nucleotide biosynthesis, fatty acid metabolism, and redox balance. Despite distinct transcriptional responses, all three viruses converge on a limited set of metabolic reactions whose flux ranges deviate strongly from healthy states. Using a network-based predictive framework, we systematically identify gene-pair perturbations that restore perturbed reaction fluxes toward non-infected metabolic states. Predicted rescue mechanisms reveal shared metabolic dependencies across coronaviruses, as well as time-dependent virus-specific vulnerabilities, and nominate druggable host targets. Notably, several top predictions align with independent experimental and clinical evidence, including metabolic interventions shown to reduce viral replication or disease severity in COVID-19 patients. Together, our results define conserved metabolic rescue pathways in coronavirus infection and provide a general strategy for identifying host-directed therapeutic opportunities from transcriptomic data. HighlightsO_LICoronaviruses converge on shared metabolic vulnerabilities in host cells C_LIO_LINiTRO predicts gene pairs that rescue viral-induced metabolic states C_LIO_LIMitochondrial transport emerges as a key pan-coronavirus target C_LIO_LITop predictions validated by clinical trials and in vitro evidence C_LI eTOC BlurbDohai et al. develop NiTRO, a network-based algorithm that integrates coronavirus-induced transcriptomic changes with genome-scale metabolic models to identify gene-pair perturbations capable of rescuing infected metabolic states. The approach reveals shared and virus-specific druggable metabolic vulnerabilities, with top predictions corroborated by clinical evidence.

systems biology↗

bioRxiv2025

Earth-Observation and Environmental Vision Transformers Reveal Genome-Environment Associations in Macroalgae

Macroalgae thrive in extreme environments, yet the genomic basis of their tolerance remains poorly resolved. We describe nine Arabian Gulf macroalgae and integrate them with 117 published genomes (126 total; 70 Rhodophyta, 43 Ochrophyta, 13 Chlorophyta) to test genome-environment associations. Google Earth Engine (GEE) for broad-scale oceanography and 10-meter resolution AlphaEarth Foundations (AEF) embeddings for fine-scale habitat heterogeneity. We identified 157 significant (FDR q < 0.05) correlations with global GEE variables--including a strong negative temperature association with DUF3570--while AEF embeddings uncovered over 1,000 lineage-specific signals within Rhodophyta and identified climate-driven Pfam modules. The von Willebrand factor type-A domain emerged as uniquely robust across all frameworks and enriched in Arabian Gulf species. In the Arabian Gulf, enrichment of this domain is consistent with selection for adhesion mechanisms capable of withstanding chronic hydrodynamic stress compounded by high temperature and salinity. These results demonstrate that converging remote sensing with deep learning identifies conserved and lineage-specific genomic signatures of ecological differentiation across diverse macroalgal lineages.

genomics↗

bioRxiv2025

Multi-omics decipher the molecular mechanisms driving high-lipid production in an artificially-evolved Chlamydomonas mutant

Enhancing lipid accumulation in microalgae is critical for commercial viability but often compromises growth. We previously identified an artificially evolved Chlamydomonas reinhardtii mutant (H5) that retains wild-type growth (CC-503) while producing significantly more lipids. Here, we present multi-omic analyses that elucidate the molecular basis of this phenotype. Whole-genome sequencing revealed over 3,000 mutations in H5, including 45 in protein-coding genes (e.g., phosphofructokinase, acyl-carrier protein, glycerol kinase). Six corresponding CLiP insertion mutants also showed elevated lipid content. Transcriptomics revealed upregulation of key genes for glycolysis, nutrient uptake, and proliferation (e.g., pyruvate carboxylase, carbonic anhydrase) under nutrient-replete conditions. Metabolomics identified a striking increase in malonate, a metabolite that supports fatty acid synthesis and cell proliferation. Epigenomic profiling showed hypomethylation in triacylglycerol (TAG) biosynthesis genes and hypermethylation in energy balance regulators. Together, these data suggest that accelerated glycolysis and streamlined metabolism drive lipid accumulation in H5 without compromising growth. Our findings provide a blueprint for engineering high-lipid microalgal strains for industrial applications. HIGHLIGHTSO_LIHigh-lipid Chlamydomonas mutant (H5) exhibits cancer-like metabolism: pseudo-hypoxia and nutrient deprivation response C_LIO_LIMulti-omics reveals 45 high-impact mutations synergistically enhance lipid production in H5 C_LIO_LISix CLiP mutants of H5-disrupted genes showed significantly increased lipid content C_LIO_LIMalonate levels increased 10-fold in H5, indicating altered mitochondrial function C_LIO_LIH5 upregulates glycolytic genes while maintaining wild-type growth rates C_LIO_LITranscriptomes from H5 and CC-503 converge after nitrogen deprivation despite replete-state differences C_LIO_LIH5 shows altered lipid composition with increased TAG diversity, decreased DAGs C_LIO_LIEpigenomic profiling reveals 14,720 differentially methylated transcribed regions in H5 C_LI

genomics↗

bioRxiv2025

Time-Resolved Transcriptomics Reveal Spliceosomal Disruption and Senescence Pathways in Crocin-Treated Hepatocellular Carcinoma Cells

Saffron-derived crocin exhibits anti-cancer properties, but the pathways underlying its effects remain incompletely characterized. Here, we utilized a high-dose perturbation strategy (1-2 mM crocin) to probe maximal pathway engagement in HepG2 hepatocellular carcinoma cells via time-series transcriptomics. We treated cells for 2, 6, 12, and 24 h and analyzed transcriptomic and splicing profiles at each timepoint. We identified 7400-12,100 differentially expressed genes (DEGs) per condition, with the higher dose (CR2) producing more total DEGs but the lower dose (CR1) demonstrating differential pathway prioritization. The spliceosome pathway ranked first among downregulated pathways for CR1 across multiple timepoints (false discovery rate, FDR p = 10-21 to 10-36) but only fourth for CR2, suggesting dose-dependent differences in pathway prioritization. Differential splicing analysis revealed functional spliceosome disruption, with 2000-2600 significant exon skipping events per condition and aberrant splicing of spliceosome components including HNRNPH1 (change in percent spliced in, dPSI = -0.78 to -0.89). Additionally, 66 genes implicated in non-alcoholic fatty liver disease were downregulated at 24 h (FDR p = 8x10-8). Crocin exposure consistently downregulated spliceosomal machinery genes while upregulating senescence and autophagy pathways. These findings identify spliceosome components and RNA processing machinery as crocin-sensitive pathways.

cancer biology↗

bioRxiv2024

A near telomere-to-telomere phased reference assembly for the male mountain gorilla

The endangered mountain gorilla, Gorilla beringei beringei, faces numerous threats to its survival, highlighting the urgent need for genomic resources to aid conservation efforts. Here, we present a near telomere-to-telomere, haplotype-phased reference genome assembly for a male mountain gorilla generated using PacBio HiFi (26.77x ave. coverage) and Oxford Nanopore Technologies (52.87x ave. coverage) data. The resulting non-scaffolded assembly exhibits exceptional contiguity, with contig N50 of [~]95 Mbp for the combined pseudohaplotype (3,540,458,497 bp), 56.5 Mbp (3.1 Gbp) and 51.0 Mbp (3.2 Gbp) for each haplotype, an average QV of 65.15 (error rate = 3.1 x 10-7), and a BUSCO score of 98.4%. These represent substantial improvements over most other available primate genomes. This first high-quality reference genome of the mountain gorilla provides an invaluable resource for future studies on gorilla evolution, adaptation, and conservation, ultimately contributing to the long-term survival of this iconic species.

genomics↗

bioRxiv2023

Identification of small molecule antivirals against HTLV-1 by targeting the hDLG1-Tax-1 protein-protein interaction

Human T-cell leukemia virus type-1 (HTLV-1) is the first pathogenic retrovirus discovered in human. Although HTLV-1-induced diseases are well characterized and linked to the encoded Tax-1 oncoprotein, there is currently no strategy to target Tax-1 functions with small molecules. Here, we analysed the binding of Tax-1 to the human homolog of the drosophila discs large tumor suppressor (hDLG1/SAP97), a multi-domain scaffolding protein involved in Tax-1-transformation ability. We have solved the structures of the PDZ binding motif (PBM) of Tax-1 in complex with the PDZ1 and PDZ2 domains of hDLG1 and assessed the binding of 10 million molecules by virtual screening. Among the 19 experimentally confirmed compounds, one systematically inhibited the Tax-1-hDLG1 interaction in different biophysical and cellular assays, as well as HTLV-1 cell-to-cell transmission in a T-cell model. Thus, our work demonstrates that interactions involving Tax-1 PDZ-domains are amenable to small-molecule inhibition, which provides a framework for the design of targeted therapies for HTLV-1-induced diseases.

biochemistry↗

bioRxiv2021

Sex-specific glycosylation of secreted immunomodulatory proteins in the filarial nematode Brugia malayi

The extended persistence of filarial nematodes within a host suggests immunomodulatory mechanisms that allow the parasites to resist or evade the host immune response. There is increasing evidence for immunomodulatory glycans expressed by a diversity of parasitic worms. In this study, we integrate multiple layers of the host-parasite interface to investigate the glycome of a model filarial parasite, Brugia malayi. We report a significant overrepresentation of terminal GalNAc moieties in adult female worms coupled with an overall upregulation in O-glycosylation, T-antigen expression, and a bias for galactose containing glycans. Adult males preferentially displayed a bias for terminal GlcNAc containing glycans, and fucosylated epitopes. Subsequent proteomic analysis confirmed sex-biases in protein glycosylation and highlighted the sex-specific glycosylation of well characterized immunomodulators expressed and secreted by B. malayi. We identify sex-specific effectors at that interface and suggest approaches to selectively interfere with the parasitic life cycle and potentially control transmission.

microbiology↗

bioRxiv2020

Exostosin-1 Glycosyltransferase Regulates Endoplasmic Reticulum Architecture and Dynamics

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of GTP nucleotides. Among post-translational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on ER structure remains unclear. Here, we show that Exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in N-glycosylation, is a key regulator of ER morphology and dynamics. We have integrated multi-omics data and super-resolution imaging to characterize the broad effect of EXT1 inactivation, including ER shape-dynamics-function relationships in mammalian cells. We have observed that, inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated to ER network extension. Our findings suggest that EXT1 drives glycosylation reactions involving ER structural proteins and high-energy nucleotide sugars, which might also apply to other organelles.

cell biology↗

bioRxiv2020

A high-quality genome assembly and annotation of the gray mangrove, Avicennia marina

The gray mangrove [Avicennia marina (Forsk.) Vierh.] is the most widely distributed mangrove species, ranging throughout the Indo-West Pacific. It presents remarkable levels of geographic variation both in phenotypic traits and habitat, often occupying extreme environments at the edges of its distribution. However, subspecific evolutionary relationships and adaptive mechanisms remain understudied, especially across populations of the West Indian Ocean. High-quality genomic resources accounting for such variability are also sparse. Here we report the first chromosome-level assembly of the genome of A. marina. We used a previously release draft assembly and proximity ligation libraries Chicago and Dovetail HiC for scaffolding, producing a 456,526,188 bp long genome. The largest 32 scaffolds (22.4 Mb to 10.5 Mb) accounted for 98 % of the genome assembly, with the remaining 2% distributed among much shorter 3,759 scaffolds (62.4 Kb to 1 Kb). We annotated 23,331 protein-coding genes using tissue-specific RNA-seq data, from which 13,312 were associated to GO terms. Genome assembly and annotated set of genes yield a 96.7% and 92.3% completeness score, respectively, when compared with the eudicots BUSCO dataset. Furthermore, an FST survey based on resequencing data successfully identified a set of candidate genes potentially involved in local adaptation, and revealed patterns of adaptive variability correlating with a temperature gradient in Arabian mangrove populations. Our A. marina genomic assembly provides a highly valuable resource for genome evolution analysis, as well as for identifying functional genes involved in adaptive processes and speciation.

genomics↗