Biology subjects

Khodadadi-Jamayran, A.

Publications and source records attributed to Khodadadi-Jamayran, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Extracellular matrix proteoglycans lumican and biglycan promote innate immune signals and viral clearance in HSV-1 infections of mouse corneas

The extracellular matrix (ECM) regulates innate immunity, but its role in HSV-1 keratitis is unclear. Here, we identify the ECM proteoglycans lumican (Lum) and biglycan (Bgn) as key regulators of early antiviral defense in the cornea. Lum-/- and BgnKO mice showed impaired viral clearance, increased corneal opacity, and worse keratitis than wild-type controls. These defects were associated with reduced early recruitment of neutrophils, monocytes, and plasmacytoid dendritic cells, and blunted induction of pro-inflammatory cytokines, chemokines, and type I interferons. In infected wild-type corneas, Lum and Bgn were upregulated, including in the basal epithelium, where Ccl2 emerged as an early epithelial response that was diminished in knockout mice. In human corneal epithelial cells, recombinant LUM or BGN enhanced HSV-1-induced CCL2 secretion, and human corneal organoids recapitulated epithelial viral tropism and CCL2 induction. Together, these findings identify Lum and Bgn as regulators of epithelial-innate immune crosstalk that promote early antiviral immunity during corneal HSV-1 infection.

immunology↗

bioRxiv2026

Autoantibodies Drive Fc Gamma Receptor-Dependent Colon Inflammation During Immune Checkpoint Blockade

Immune checkpoint inhibitor (ICI)-associated colitis limits effective cancer immunotherapy, yet host determinants of severe toxicity remain undefined. We investigated whether humoral immunity is associated with subsequent severe immune-related colitis (irC). In melanoma patients, baseline serum autoantibody (AAb) profiling identified a composite antigen signature - a signature-level association rather than validated functional specificities - associated with severe irC, marked by retained reactivity to tumor-associated antigens and relative depletion of antibodies recognizing immune- and mucosal-regulatory proteins. To assess functional relevance, we transferred polyclonal IgG from severe- or non-severe-irC patients into wild-type or humanized Fc{gamma} receptor (hFc{gamma}R) mice treated with anti-PD-1 or anti-CTLA-4. IgG alone did not induce inflammation; however, severe-irC IgG amplified checkpoint-driven colonic inflammation in hFc{gamma}R mice, but not in wild-type mice, with checkpoint-specific remodeling of myeloid, lymphoid, and innate lymphoid compartments. These findings suggest that pretreatment humoral immunity conditions susceptibility to irC via the IgG-Fc{gamma}R axis.

cancer biology↗

bioRxiv2025

Persistent Classical and Atypical Memory B Cells Underlie Heterogeneous Vaccine Responses in Ocrelizumab-Treated Multiple Sclerosis

Background and ObjectivesPatients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR), a B-cell-depleting therapy, exhibit heterogeneous humoral responses to SARS-CoV-2 mRNA vaccination. The mechanisms underlying this variability remain incompletely understood. We performed a longitudinal analysis of B-cell subset dynamics and antigen-specific T cell responses in OCR-treated pwMS and healthy controls to determine how immune cell composition, timing of OCR infusion, and lymphocyte dynamics influence humoral response outcomes. MethodsBased on post-vaccination anti-Spike IgG titers measured by multiplex bead immunoassay, pwMS were categorized as super-responders (SR), responders (R), or non-responders (NR). A 35-marker spectral flow cytometry panel was used to characterize T- and B-cell subsets longitudinally, at baseline and following stimulation with a SARS-CoV-2 peptide pool. ResultsCD4+ and CD8+ T cell populations were preserved across OCR-treated pwMS, and SARS-CoV-2-specific T cells remained detectable for more than 6 months after vaccination. In contrast, residual B-cell subset composition distinguished responders from non-responders. DN2-like B cells (CD19+CD27-IgD-T-bet+CD11c+CXCR5-) persisted despite repeated OCR infusions and were enriched in SR compared with NR. Repletion of mature naive B cells in peripheral blood correlated with time since last OCR infusion and with stronger humoral immune responses. ConclusionsB-cell subsets that resist OCR-mediated depletion may contribute to vaccine responsiveness in OCR-treated pwMS. Altered repletion kinetics of naive B cell subsets in non-responders suggest that specific B-cell populations may serve as predictive biomarkers of vaccine-induced humoral immunity, despite preserved T-cell responses.

immunology↗

bioRxiv2025

Dicer is essential for proper maturation, composition, and function in the postnatal retina.

microRNAs (miRNAs) play a pivotal role during the early phases of retinal development, but their impact on late-phase retinogenesis is unknown. We depleted miRNAs in late retinal progenitor/precursor cells (RPCs/PCs) via a conditional Dicer knock-out. Optical coherence tomography (OCT), electroretinography (ERG), histological, and transcriptional analyses were conducted in young and adult mice. Alterations in gene expression of late-born cells were observed as early as postnatal day 7 (P7), resulting in impaired rod function, a significantly reduced number of rod bipolar cells and their associated function, and a decreased Muller glia population at adult age. These defects appear to be caused by a delay in differentiation/ incomplete maturation, as indicated by an enlarged progenitor/precursor population at young ages that persists into adulthood. Notably, an increased population of HuC/D+ amacrine cells was found. Luciferase assays led us to speculate that this increase may be due to the absence of Elavl3 suppression via RPC-miRNAs. This suggests that Dicer/miRNAs in late RPC/PCs are essential for the proper formation and maturation of late RPC progenies and may also play a role in regulating cell state. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/635135v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@9e0950org.highwire.dtl.DTLVardef@1757e2corg.highwire.dtl.DTLVardef@aeb5ecorg.highwire.dtl.DTLVardef@29accb_HPS_FORMAT_FIGEXP M_FIG C_FIG Summary statementLate-retinal progenitor microRNAs are essential for proper postnatal retinogenesis and retinal function.

developmental biology↗

bioRxiv2025

Regulating white blood cell activity through the novel Universal Receptive System

The understanding of the mechanisms that control key features of immune cells in various disease contexts remains limited, and few techniques are available for manipulating immune cells. Thus, discovering novel strategies for regulating immune cells is essential for gaining insight into their roles in health and disease. In this study, we investigated the potential of the recently described Universal Receptive System to regulate human immune cell functions. This was achieved for the first time by specifically targeting newly discovered surface-bound DNA and RNA-based receptors on leukocytes and generating "Leukocyte-Tells." This approach upregulated numerous genes related to immune cell signaling, migration, endocytosis, and phagocytosis pathways. The antimicrobial and anticancer activities of Leukocyte-Tells exceeded the activity of control leukocytes in vitro. In some settings, such as in antibiofilm experiments, the Leukocyte-Tells showed up to 1,000,000-fold higher activities than control leukocytes. Our findings reveal, for the first time, that the Universal Receptive System can orchestrate fundamental properties of immune cells, including enhanced antimicrobial and anti-tumor activities. This novel approach offers a new avenue for understanding the biology and regulation of white blood cells.

immunology↗

bioRxiv2024

The Universal Receptive System acts as a novel regulator in the production of antimicrobial and anticancer bioactive compounds by white blood cells

Despite recent advances, the regulation of anticancer and antimicrobial bioactive compound (AABC) production by leukocytes remains poorly understood. Here, we demonstrate that inactivation of the DNA- and RNA-based Teazeled receptors of the Universal Receptive System in human leukocytes generated so called "Leukocyte-Tells," which showed enhanced AABC production. Comprehensive analysis of the AABCs produced by Leukocyte-Tells based on LC/MS identified 707 unique or differentially produced peptide or non-peptide metabolites. Functional testing demonstrated that many of these metabolites exhibited increased antibacterial, antifungal, and anticancer activities. The AABCs produced by the Leukocyte-Tells were effective against different multidrug-resistant clinical isolates of fungi and gram-positive and gram-negative bacteria (including their biofilms), as well as various cancer cell lines, with >100,000-fold activity than AABCs derived from control leukocytes. Notably, the AABCs produced by the Leukocyte-Tells exhibited greater stability under adverse environmental conditions. Our findings highlight the important role of the Universal Receptive System in regulating AABC production through a process named here as cell genome memory management, offering new insights into immune functions and suggesting potential therapeutic applications. SummaryThe Universal Receptive System acts as a novel regulator of biosynthetic activity in leukocytes. Modulating the leukocyte Universal Receptive System by inactivating Teazeled receptors triggers the production of new compounds not observed in naive cells. We refer to these TezR-modified cells as "Leukocyte-Tells." Leukocytes produce unique metabolites with strong anticancer and antimicrobial activities. Reproducibility in generating leukocytes from the blood of different donors suggests that the observed alterations in cell activity were preprogrammed.

molecular biology↗

bioRxiv2024

Universal Receptive System as a novel regulator of transcriptomic activity of Staphylococcus aureus

Our previous studies revealed the existence of a Universal Receptive System that regulates interactions between cells and their environment. This system is composed of DNA- and RNA-based Teazeled receptors (TezRs) found on the surface of prokaryotic and eukaryotic cells, as well as integrases and recombinases.. In the current study, we aimed to provide further insight into the regulatory role of TezR and its loss in Staphylococcus aureus gene transcription. To this end, transcriptomic analysis of S. aureus MSSA VT209 was performed following the destruction of TezRs. Bacterial RNA samples were extracted from nuclease-treated and untreated S. aureus MSSA VT209. After destruction of the DNA-based-, RNA-, or combined DNA- and RNA-based TezRs of S. aureus, 103, 150, and 93 genes were significantly differently expressed, respectively. The analysis revealed differential clustering of gene expression following the loss of different TezRs, highlighting individual cellular responses following the loss of DNA- and RNA-based TezRs. KEGG pathway gene enrichment analysis revealed that the most upregulated pathways following TezR inactivation included those related to energy metabolism, cell wall metabolism, and secretion systems. Some of the genetic pathways were related to the inhibition of biofilm formation and increased antibiotic resistance, and we confirmed this at the phenotypic level using in vitro studies. The results of this study add another line of evidence that the Universal Receptive System plays an important role in cell regulation, including cell responses to the environmental factors of clinically important pathogens, and that nucleic acid-based TezRs are functionally active parts of the extrabiome.

microbiology↗

bioRxiv2024

Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells

The cohesin protein complex extrudes chromatin loops, stopping at CTCF-bound sites, to organize chromosomes into topologically associated domains, yet the biological implications of this process are poorly understood. We show that cohesin is required for the post-mitotic differentiation and function of antigen-presenting dendritic cells (DCs), particularly for antigen cross-presentation and IL-12 secretion by type 1 conventional DCs (cDC1s) in vivo. The chromatin organization of DCs was shaped by cohesin and the DC-specifying transcription factor IRF8, which controlled chromatin looping and chromosome compartmentalization, respectively. Notably, optimal expression of IRF8 itself required CTCF/cohesin-binding sites demarcating the Irf8 gene. During DC activation, cohesin was required for the induction of a subset of genes with distal enhancers. Accordingly, the deletion of CTCF sites flanking the Il12b gene reduced IL-12 production by cDC1s. Our data reveal an essential role of cohesin-mediated chromatin regulation in cell differentiation and function in vivo, and its bi-directional crosstalk with lineage-specifying transcription factors.

immunology↗

bioRxiv2024

Previously unknown regulatory role of extracellular RNA on bacterial directional migration

Bacterial directional migration plays a significant role in bacterial adaptation. However, the regulation of this process, particularly in young biofilms, remains unclear. Here, we demonstrated the critical role of extracellular RNA as part of the Universal Receptive System in bacterial directional migration using a multidisciplinary approach, including bacterial culture, biochemistry, and genetics. We found that the destruction or inactivation of extracellular RNA with RNase or RNA-specific antibodies in the presence of the chemoattractant triggered the formation of bacterial "runner cells>> in what we call a "panic state" capable of directional migration. These cells quickly migrated even on the surface of 1.5% agar and formed evolved colonies that were transcriptionally and biochemically different from the ancestral cells. We have also shown that cell-free DNA from blood plasma can act as a potent bacterial chemoattractant. Our data revealed a previously unknown role of bacterial extracellular RNA in the regulation of bacterial migration and have shown that its destruction or inhibition triggered the directional migration of developing and mature biofilms towards the chemoattractant.

microbiology↗

bioRxiv2023

The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability

Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their functional role in gliomagenesis and their potential as treatment targets. To identify therapeutically targetable opportunities among aGPCR family members in unbiased fashion, we analyzed expression levels of all aGPCRs in GBM and non-neoplastic brain tissue. Using bulk and single cell transcriptomic and proteomic data, we show that CD97 (ADGRE5), an aGPCR previously implicated in GBM pathogenesis, is the most promising aGPCR target in GBM, by virtue of its abundance in all GBM tumors and its de novo expression profile in GBM compared to normal brain tissue and neural progenitors. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures (PDGC) in vitro and in vivo. Transcriptomic and metabolomic data from PDGCs suggest that CD97 promotes glycolytic metabolism. The oncogenic and metabolic effects of CD97 are mediated by the MAPK pathway. Activation of MAPK signaling depends on phosphorylation of the cytosolic C-terminus of CD97 and recruitment of {beta}-arrestin. Using single-cell RNA-sequencing and biochemical assays, we demonstrate that THY1/CD90 is the most likely CD97 ligand in GBM. Lastly, we show that targeting of PDGCs with an anti-CD97 antibody-drug conjugate in vitro selectively kills tumor cells but not human astrocytes or neural stem cells. Our studies identify CD97 as an important regulator of tumor metabolism in GBM, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target it for therapeutic purposes.

cancer biology↗

bioRxiv2022

De novo assembly and annotation of the singing mouse genome

BackgroundDeveloping genomic resources for a diverse range of species is an important step towards understanding the mechanisms underlying complex traits.Specifically, organisms that exhibit unique, accessible phenotypes-of-interests, allow researchers to address questions that may be ill-suited to traditional model organisms. We sequenced the genome and transcriptome of Alstons singing mouse (Scotinomys teguina), an emerging model for social cognition and vocal communication. In addition to producing advertisement songs used for mate attraction and male-male competition, these rodents are diurnal, live at high-altitudes, and are obligate insectivores, providing opportunities to explore diverse physiological, ecological, and evolutionary questions. ResultsUsing PromethION, Illumina, and PacBio sequencing, we produced an annotated genome and transcriptome, which were validated using gene expression and functional enrichment analyses. To assess the usefulness of our assemblies, we performed single nuclei sequencing on cells of the orofacial motor cortex, a brain region implicated in song coordination, identifying 12 cell types. ConclusionsThese resources will provide the opportunity to identify the molecular basis of complex traits in singing mice as well as to contribute data that can be used for large-scale comparative analyses.

genomics↗

bioRxiv2022

Genome-wide analysis of dendritic cell differentiation

Dendritic cells (DCs) are immune sentinel cells that comprise antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs). Cytokine Flt3 ligand (Flt3L) supports the proliferation of hematopoietic progenitors, and is also necessary and sufficient for DC differentiation. Here we characterized the spontaneous differentiation of a Flt3L-dependent murine progenitor cell line into pDCs and "myeloid" cDCs (cDC2s), and interrogated it using a genome-wide CRISPR/Cas9 dropout screen. The screen revealed multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex, the Nieman-Pick type C cholesterol transporter and arginine methyltransferase Carm1; the role of Carm1 in pDC and cDC2 differentiation was confirmed by conditional targeting in vivo. We also found that negative regulators of mTOR signaling, including the subunits of TSC and GATOR1 complexes, restricted progenitor growth but enabled DC differentiation. The results provide a comprehensive forward genetic analysis of DC differentiation, and help explain how the opposing processes of proliferation and differentiation could be driven by the same cytokine.

immunology↗

bioRxiv2021

PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function

Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We unexpectedly found that PRC2 is dispensable to preserve the morphogen-induced positional fates of spinal motor neurons (MNs), while PRC1 is essential for the specification of segmentally-restricted subtypes. Mutation of the core PRC1 component Ring1 in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities in Ring1 mutants is due to the suppression of Hox networks by derepressed caudal Hox genes. These results indicate that PRC1 can function independently of de novo PRC2-dependent histone methylation to maintain chromatin topology and transcriptional memory at the time of neuronal differentiation.

neuroscience↗

bioRxiv2021

Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC

Clinical trials of SHP2 inhibitors (SHP2i) alone and in various combinations are ongoing for multiple tumors with over-activation of the RAS/ERK pathway. SHP2 plays critical roles in normal cell signaling; hence, SHP2is could influence the tumor microenvironment. We found that SHP2i treatment depleted alveolar and M2-like macrophages and promoted B and T lymphocyte infiltration in Kras- and Egfr-mutant non-small cell lung cancer (NSCLC). However, treatment also increased intratumor gMDSCs via tumor-intrinsic, NF-kB-dependent production of CXCR2 ligands. Other RAS/ERK pathway inhibitors also induced CXCR2 ligands and gMDSC influx in mice, and CXCR2 ligands were induced in tumors from patients on KRASG12C-inhibitor trials. Combined SHP2(SHP099)/CXCR1/2(SX682) inhibition depleted a specific cluster of S100a8/9high gMDSCs, generated Klrg1+ CD8+ effector T cells with a strong cytotoxic phenotype but expressing the checkpoint receptor NKG2A, and enhanced survival in Kras-and Egfr-mutant models. Our results argue for testing RAS/ERK pathway/CXCR1/2/NKG2A inhibitor combinations in NSCLC patients. Statement of SignificanceOur study shows that inhibiting the SHP2/RAS/ERK pathway triggers NF-kB-dependent up-regulation of CXCR2 ligands and recruitment of S100A8high gMDSCs, which suppress T cells in NSCLC. Combining SHP2 and CXCR2 inhibitors blocks this gMDSC immigration, resulting in enhanced Th1 polarization, induction of CD8+ KLRG1+ effector T cells with high cytotoxic activity and improved survival in multiple NSCLC models.

cancer biology↗

bioRxiv2020

Ontogeny and Vulnerabilities of Lapatinib Drug-Tolerant Persisters in HER2+ Breast Cancer

Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. "Drug-tolerant persisters" (DTPs), a sub-population of cancer cells that survive via reversible, non-genetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKIs) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome. Lentiviral barcoding/single cell RNA-sequencing reveal that HER2+ breast cancer cells cycle stochastically through a "pre-DTP" state, characterized by a G0-like expression signature and enriched for diapause and/or senescence genes. Trajectory analysis/cell sorting show that pre-DTPs preferentially yield DTPs upon HER2 TKI exposure. Cells with similar transcriptomes are present in HER2+ breast tumors and are associated with poor TKI response. Finally, biochemical experiments indicate that luminal-like DTPs survive via estrogen receptor-dependent induction of SGK3,leading to rewiring of the PI3K/AKT/mTORC1 pathway to enable AKT-independent mTORC1 activation. STATEMENT OF SIGNIFICANCEDTPs are implicated in resistance to TKIs, other targeted therapies, and chemotherapy, but their ontogeny and vulnerabilities remain unclear. We find that HER2 TKI-DTPs emerge from stochastically arising primed cells ("pre-DTPs") that preferentially engage either of two distinct transcriptional programs upon TKI exposure. Our results provide new insights into DTP ontogeny and identify potential therapeutic vulnerabilities.

cancer biology↗

bioRxiv2020

Graph Drawing-based Dimensionality Reduction to Identify Hidden Communities in Single-Cell Sequencing Spatial Representation

With the rapid growth of single cell sequencing technologies, finding cell communities with high accuracy has become crucial for large scale projects. Employing the current commonly used dimensionality reduction techniques such as tSNE and UMAP, it is often difficult to clearly distinguish cell communities in high dimensional space. Usually cell communities with similar origin and trajectories cluster so closely to each that their subtle but important differences do not become readily apparent. This creates a problem for clustering, as clustering is also performed on dimensionality reduction results. In order to identify such communities, scientists either perform broad clustering and then extract each cluster and perform re-clustering to identify sub-populations or they over-cluster the data and then merging the clusters with similar gene expressions. This is an incredibly cumbersome and time-consuming process. To solve this problem, we propose K-nearest-neighbor-based Network graph drawing Layout (KNetL, pronounced like nettle) for dimensionality reduction. In our method, we use force-directed graph drawing, whereby the attractive force (analogous to a spring force) and the repulsive force (analogous to an electrical force in atomic particles) between the cells are evaluated, and the cell communities are organized in a structural visualization. The coordinates of the force-compacted nodes are then extracted, and we employ dimensionality reduction methods, such as tSNE and UMAP to unpack the nodes. The final plot, a KNetL map, shows a visually-appealing and distinctive separation between cell communities. Our results show that KNetL maps bring significant resolution to visualizing and identifying otherwise hidden cell communities. All the algorithms are implemented in the iCellR package and available through the CRAN repository. Single (i) Cell R package (iCellR) provides great flexibility at every step of the analysis pipeline, including normalization, clustering, dimensionality reduction, interactive 2D and 3D visualizations, batch alignment or data integration, imputation, and interactive cell gating tools, which allow users to manually gate around the cells.

bioinformatics↗

bioRxiv2020

Defining Epidermal Stem Cell Fate Infidelity and Immunogenicity in Hidradenitis Suppurativa at the Single-Cell Resolution

Hidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease affecting human apocrine sweat gland-bearing skin regions. One unique feature of HS is the development of keratinized sinus tracts that grow extensively deep in the dermis and are highly immunogenic. Here, we demonstrated that the stem cell fate infidelity exists in the HS sinus tracts, which exhibit features of both surface epidermis and appendages. Using single cell transcriptome analyses, we finely dissected different compartments of the HS epithelium and identified their respective changes in cytokine expression during disease progression and the critical interactions with the immune cells. Together, our work provides advanced understanding of the pathological epidermal remodeling and important implications for HS therapeutics.

cell biology↗

bioRxiv2020

iCellR: Combined Coverage Correction and Principal Component Alignment for Batch Alignment in Single-Cell Sequencing Analysis

Under-sampling RNA molecules and low-coverage sequencing in some single cell sequencing technologies introduce zero counts (also known as drop-outs) into the expression matrices. This issue may complicate the processes of dimensionality reduction and clustering, often forcing distinct cell types to falsely resemble one another, while eliminating subtle, but important differences. Considering the wide range in drop-out rates from different sequencing technologies, it can also affect the analysis at the time of batch/sample alignment and other downstream analyses. Therefore, generating an additional harmonized gene expression matrix is important. To address this, we introduce two separate batch alignment methods: Combined Coverage Correction Alignment (CCCA) and Combined Principal Component Alignment (CPCA). The first method uses a coverage correction approach (analogous to imputation) in a combined or joint fashion between multiple samples for batch alignment, while also correcting for drop-outs in a harmonious way. The second method (CPCA) skips the coverage correction step and uses k nearest neighbors (KNN) for aligning the PCs from the nearest neighboring cells in multiple samples. Our results of nine scRNA-seq PBMC samples from different batches and technologies shows the effectiveness of both these methods. All of our algorithms are implemented in R, deposited into CRAN, and available in the iCellR package.

bioinformatics↗