Biology subjects

Thomas, A.

Publications and source records attributed to Thomas, A..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

A brainstem map of orofacial rhythms

Rhythmic orofacial movements, such as eating, drinking, or vocalization, are controlled by distinct premotor oscillator networks in the brainstem. Orofacial movements must be coordinated with rhythmic breathing to avoid aspiration and because they share muscles. Understanding how brainstem circuits coordinate rhythmic motor programs requires neurophysiological measurements in behaving animals. We used Neuropixels probe recordings to map brainstem neural activity related to breathing, licking, and swallowing in mice drinking water. Breathing and licking rhythms were tightly coordinated and phase-locked, whereas intermittent swallowing paused breathing and licking. Multiple clusters of neurons, each recruited during different orofacial rhythms, delineated a lingual premotor network in the intermediate nucleus of the reticular formation (IRN). Local optogenetic perturbation experiments identified a region in the IRN where constant stimulation can drive sustained rhythmic licking, consistent with a central pattern generator for licking. Stimulation to artificially induce licking showed that coupled brainstem oscillators autonomously coordinated licking and breathing. The brainstem oscillators were further patterned by descending inputs at moments of licking initiation. Our results reveal the logic governing interactions of orofacial rhythms during behavior and outline their neural circuit dynamics, providing a model for dissecting multi-oscillator systems controlling rhythmic motor programs.

neuroscience↗

bioRxiv2025

ERGA-BGE genome of Cheirolophus tagananensis: an IUCN endangered shrub endemic to the Canary Islands

The reference genome of Cheirolophus tagananensis, locally known as the Cabezon de Taganana, will provide an exceptional opportunity to establish a new framework to develop comparative genomic tools. These tools will help uncover the genetic basis of rapid plant radiations and microevolutionary adaptation processes of insular species on oceanic islands. This genomic resource will also contribute to facilitate the establishment of better informed in situ and ex-situ conservation strategies for this narrow endemic in the face of potential habitat degradation, and support taxonomic studies to better understand genetic diversity at the population, species, and genus levels. A total of 16 contiguous chromosomal pseudomolecules were assembled from the genome sequence. This chromosome-level assembly encompasses 0.62 Gb, composed of 421 contigs and 235 scaffolds, with contig and scaffold N50 values of 4.0 Mb and 36.5 Mb, respectively.

genomics↗

bioRxiv2025

RNA-triggered CRISPR-Cas12a2 Preferentially and Cooperatively Cleaves Collateral DNA

CRISPR-Cas systems often rely on collateral cleavage of nucleic-acid substrates to combat recognized mobile genetic elements. Of the CRISPR-associated (Cas) RNA-guided effector nucleases, Cas12a2 stands out as the only known example exhibiting rapid collateral cleavage of three distinct substrates: single-stranded (ss)RNA, ssDNA, and double-stranded (ds)DNA, after activating upon binding cognate RNA. However, little is known about the underlying mechanisms of collateral cleavage. Here, we show, using enzyme kinetics and inhibition assays, that Cas12a2 preferentially cleaves collateral DNA over RNA substrates, even when RNA substrates are more abundant. Additionally, using enzyme mutants, enzyme kinetics, and plasmid cleavage assays, we determine that the dsDNA cleavage mechanism relies on the aromatic clamp residues that stabilize unwound and distorted dsDNA in the RuvC nuclease active site. Leveraging the cleavage preference for collateral DNA, we demonstrate that RNA-activated Cas12a2 can readily cleave a ssDNA probe in the presence of high concentrations of non-target RNA, while an RNA-targeting Cas13a cannot. This work provides foundational kinetic and biochemical insights into the collateral cleavage mechanism and substrate preferences of Cas12a2, with immediate implications for understanding Cas12a2-based immunity and developing Cas12a2-based technologies.

biochemistry↗

bioRxiv2024

ENaC contributes to macrophage dysfunction in cystic fibrosis

BackgroundCystic fibrosis (CF) is a chronic systemic disease caused by dysfunctional or absent cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is expressed in human immune cells and plays a role in regulating innate immunity both directly and indirectly. Besides CFTR, research indicates that the epithelial sodium channel (ENaC) also contributes to dysfunction in CF airway epithelial cells. However, the impact of non-CFTR ion channel dysfunction on CF immune responses is not yet fully understood. A precise understanding of how CF immune function is regulated by ion channels may allow antibiotic-and mutation-agnostic treatment approaches to chronic bacterial infection and inflammation. Therefore, we hypothesized that ENaC is aberrantly expressed in CF macrophages and directly contributes to impaired phagocytic and inflammatory functions. MethodsENaC expression was characterized in human immune cells isolated from CF and non-CF blood donors. Monocyte-derived macrophage (MDM) function and bacterial killing was tested in the setting of ENaC modulation. ResultsBaseline expression of ENaC in human CF MDMs, lymphocytes, and granulocytes was increased at both the transcript and protein level relative to non-CF controls and persisted after exposure to bacteria. Inhibition of CFTR in non-CF MDMs resulted in ENaC overexpression. CFTR modulator treatment reduced but did not eliminate ENaC overexpression in CF MDMs. Interestingly, ENaC inhibition with Amiloride increased CFTR expression. Amiloride-treated CF MDMs also showed normalized ROS production, improved autophagy, and decreased pro-inflammatory cytokine production. Finally, results from an ion channel microarray indicated that sodium channel expression in CF MDMs normalized after Amiloride treatment with minimal effect on other ion channels. DiscussionENaC is overexpressed in CF immune cells and is associated with abnormal macrophage function. ENaC modulation in immune cells is a novel potential therapeutic target for infection control in CF, either in combination with CFTR modulators, or as a sole agent for patients not currently eligible for CFTR modulators.

immunology↗

bioRxiv2024

Metastatic organotropism in small cell lung cancer

Metastasis is the leading cause of cancer-related deaths, yet its regulatory mechanisms are not fully understood. Small-cell lung cancer (SCLC) is the most metastatic form of lung cancer, with most patients presenting with widespread disease, making it an ideal model for studying metastasis. However, the lack of suitable preclinical models has limited such studies. We utilized rapid autopsy-derived tumors to develop xenograft models that mimic key features of SCLC, including histopathology, rapid and widespread development of metastasis to the liver, brain, adrenal, bone marrow, and kidneys within weeks, and response to chemotherapy. By integrating in vivo lineage selection with comprehensive bulk and single cell multiomic profiling of transcriptomes and chromatin accessibility, we identified critical cellular programs driving metastatic organotropism to the liver and brain, the most common sites of SCLC metastasis. Our findings reveal the key role of nuclear-cytoskeletal interactions in SCLC liver metastasis. Specifically, the loss of the nuclear envelope protein lamin A/C, encoded by the LMNA gene, increased nuclear deformability and significantly increased the incidence of liver metastasis. Human liver metastases exhibited reduced LMNA expression compared to other metastatic sites, correlating with poorer patient outcomes and increased mortality. This study introduces novel preclinical models for SCLC metastasis and highlights pathways critical for organ-specific metastasis, offering new avenues for the development of targeted therapies to prevent or treat metastatic disease.

cancer biology↗

bioRxiv2024

Harnessing light heterogeneity to optimise controlled environment agriculture

Yield is impacted by the environmental conditions that plants are exposed to. Controlled environmental agriculture provides growers with an opportunity to fine-tune environmental conditions for optimising yield and crop quality. However, space and time constraints will limit the number of experimental conditions that can be tested, which will in turn limit the resolution to which environmental conditions can be optimised. Here we present an innovative experimental approach that utilises the existing heterogeneity in light quantity and quality across a vertical farm to evaluate hundreds of environmental conditions concurrently. It proposes a three-phase workflow for identifying critical light variables, which can guide targeted improvements in yield and energy use. Using an observational study design, we identify features in light quality that are most predictive of biomass in different microgreens crops (kale, radish and sunflower) that may inform future iterations of lighting technology development for vertical farms. The findings suggest that light quality, rather than just light intensity, plays a crucial role in uniform crop yields and that light sensitivities are variety-specific, highlighting the importance of tailored light recipes for different crops.

plant biology↗

bioRxiv2024

Transcriptomic alterations including p53 pathway dysregulation prime DNMT3A mutant cells for transformation

DNMT3A mutations are prevalent in haematologic malignancies. Our mouse model introduced the murine homologue (R878H) of the human hotspot R882H mutation into the mouse Dnmt3a locus, resulting in globally reduced DNA methylation in all tissues. Mice with heterozygous R878H mutations developed {gamma}-radiation induced thymic lymphoma more rapidly than control mice, suggesting a vulnerability to stress stimuli in Dnmt3aR878H/+ cells. In competitive transplantations, Dnmt3aR878H/+ Lin-Sca-1+Kit+ (LSK) cells had a competitive advantage over wt cells, indicating a self-renewal phenotype at the expense of differentiation. RNA-sequencing of Dnmt3aR878H/+ LSKs exposed to low dose {gamma}-radiation showed downregulation of the p53 pathway. Accordingly, reduced PUMA expression was observed by flow cytometry in the bone marrow of {gamma}-irradiated Dnmt3aR878H/+ mice due to altered p53 signalling. These findings provide new insights as to how DNMT3A mutations cause subtle changes in the transcriptome of LSK cells which contribute to their increased self-renewal and propensity for malignant transformation. SIGNIFICANCEHotspot DNMT3A R882H mutations are overrepresented in leukaemia suggesting that they confer a susceptibility to disease if further mutations are acquired. To advance therapies for DNMT3A mutant disease, it is essential to understand the mechanisms by which this mutation primes cells for malignant transformation.

cancer biology↗

bioRxiv2024

Identification of CNTN2 as a genetic modifier of PIGA-CDG through pedigree analysis of a family with incomplete penetrance and functional testing in Drosophila

Loss of function mutations in the X-linked PIGA gene lead to PIGA-CDG, an ultra-rare congenital disorder of glycosylation (CDG), typically presenting with seizures, hypotonia, and neurodevelopmental delay. We identified two brothers (probands) with PIGA-CDG, presenting with epilepsy and mild developmental delay. Both probands carry PIGAS132C, an ultra-rare variant predicted to be damaging. Strikingly, the maternal grandfather and a great-uncle also carry PIGAS132C, but neither presents with symptoms associated with PIGA-CDG. We hypothesized genetic modifiers may contribute to this reduced penetrance. Using whole genome sequencing and pedigree analysis, we identified possible susceptibility variants found in the probands and not in carriers and possible protective variants found in the carriers and not in the probands. Candidate variants included heterozygous, damaging variants in three genes also involved directly in GPI-anchor biosynthesis and a few genes involved in other glycosylation pathways or encoding GPI-anchored proteins. We functionally tested the predicted modifiers using a Drosophila eye-based model of PIGA-CDG. We found that loss of CNTN2, a predicted protective modifier, rescues loss of PIGA in Drosophila eye-based model, like what we predict in the family. Further testing found that loss of CNTN2 also rescues patient-relevant phenotypes, including seizures and climbing defects in Drosophila neurological models of PIGA-CDG. By using pedigree information, genome sequencing, and in vivo testing, we identified CNTN2 as a strong candidate modifier that could explain the incomplete penetrance in this family. Identifying and studying rare disease modifier genes in human pedigrees may lead to pathways and targets that may be developed into therapies.

genetics↗

bioRxiv2024

Fig4 confers tolerance to rapamycin in a Ste20-dependent manner independent of the Vac14 scaffold

Summary StatementDisease-related Fig4 mutants displaying impaired association with the Fab1-Vac14-Fig4 complex confer tolerance to rapamycin in Saccharomyces cerevisiae independent of Vac14 in a Ste20-dependent manner. Fig4 can thus modulate homeostasis through association with pathways outside of the Fab1-Vac14-Fig4 complex in yeast. The lipid phosphatase Fig4 modulates the production and turnover of the signaling lipid PI3,5P2 through participation in a complex with its opposing kinase, Fab1, and the scaffold protein Vac14. Fig4 point mutations are associated with neurological diseases for which there are currently no specific therapies. Pathology involving Fig4 is generally attributed to disruption of the Fab1-Vac14-Fig4 complex. Through genetic manipulations in yeast we show that expression of Fig4 disease-related mutants confers tolerance to rapamycin, an inhibitor of the master growth activator TORC1. This phenotype is dominantly conferred at high temperatures by Fig4 mutants that bind poorly to Vac14 or by excess wild-type Fig4. Rapamycin tolerance does not require Fig4 catalytic activity or Vac14, suggesting that Fig4 mediates this altered stress response through context-inappropriate binding interactions with unknown proteins. The p21-activated kinase Ste20 is specifically required for this novel Vac14-independent Fig4 function. Our study shows that Fig4 can modulate homeostasis in Saccharomyces cerevisiae through interactions outside the Fab1-Vac14-Fig4 complex.

cell biology↗

bioRxiv2024

IgM plays a prominent role in naturally acquired immunity against Plasmodium falciparum gametocytes

The development of transmission-blocking vaccines against Plasmodium falciparum malaria could facilitate malaria elimination. However, limitations in the knowledge of the human immune responses against P. falciparum transmission stages, known as gametocytes, represent a critical roadblock to vaccine development. We evaluated human antibodies acquired through natural malaria exposure to whole gametocytes and recombinant antigens expressed by transmission stages, including the major transmission-blocking vaccine candidates Pfs230 and Pfs48/45 and other transmission stages, Pf38, Pf12 and Pf41. Among individuals residing in Kenya and Papua New Guinea, we found substantial antibody responses to whole gametocytes and to all recombinant transmission stage antigens with high levels of IgG, IgG subclasses and IgM. Complement fixation by antibodies to gametocytes is key for effective transmission-blocking activity. We found that purified IgM was substantially more potent than IgG at mediating complement fixation and activation. Higher antibody levels were generally observed in individuals positive for P. falciparum infection, including gametocyte positive individuals, and these antibodies generally increased with age. Our findings reveal that IgM is a prominent feature of antibody responses to gametocytes and that antibodies target multiple antigens. The further demonstration that IgM has high functional activity against gametocytes suggests IgM plays an important role in immunity to transmission stages. Our data provide new insights to inform the development of potent transmission-blocking vaccines.

immunology↗

bioRxiv2024

Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

Our study elucidates functional roles for conserved cis-elements associated with the evolution of mammalian hibernation. Genomic analyses found topologically associated domains (TADs) that disproportionately accumulated convergent genomic changes in hibernators, including the TAD for the Fat Mass & Obesity (Fto) locus. Some hibernation-linked cis-elements in this TAD form regulatory contacts with multiple neighboring genes. Knockout mice for these cis-elements exhibit Fto, Irx3, and Irx5 gene expression changes, impacting hundreds of genes downstream. Profiles of pre-torpor, torpor, and post-torpor phenotypes found distinct roles for each cis-element in metabolic control, while a high caloric diet uncovered different obesogenic effects. One cis-element promoting a lean phenotype influences foraging behaviors throughout life, affecting specific behavioral sequences. Thus, convergent evolution in hibernators pinpoints functional genetic mechanisms of mammalian metabolic control. One-sentence summaryDeletions of conserved cis-elements tied to hibernator evolution causes diverse metabolic traits in mice.

genomics↗

bioRxiv2024

A genetically encoded sensor for real-time monitoring of poly-ADP-ribosylation dynamics in-vitro and in cells

ADP-ribosylation, the transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) groups to proteins, is a conserved post-translational modification (PTM) that occurs most prominently in response to DNA damage. ADP-ribosylation is a dynamic PTM regulated by writers (PARPs), erasers (ADPr hydrolases), and readers (ADPR binders). PARP1 is the primary DNA damage-response writer responsible for adding a polymer of ADPR to proteins (PARylation). Real-time monitoring of PARP1-mediated PARylation, especially in live cells, is critical for understanding the spatial and temporal regulation of this unique PTM. Here, we describe a genetically encoded FRET probe (pARS) for semi-quantitative monitoring of PARylation dynamics. pARS feature a PAR-binding WWE domain flanked with turquoise and Venus. With a ratiometric readout and excellent signal-to-noise characteristics, we show that pARS can monitor PARP1-dependent PARylation temporally and spatially in real-time. pARS provided unique insights into PARP1-mediated PARylation kinetics in vitro and high-sensitivity detection of PARylation in live cells, even under mild DNA damage. We also show that pARS can be used to determine the potency of PARP inhibitors in vitro and, for the first time, in live cells in response to DNA damage. The robustness and ease of use of pARS make it an important tool for the PARP field.

biochemistry↗

bioRxiv2024

Genomic alterations and transcriptional phenotypes in circulating tumor DNA and matched metastatic tumor

BackgroundProfiling circulating cell-free DNA (cfDNA) has become a fundamental practice in cancer medicine, but the effectiveness of cfDNA at elucidating tumor-derived molecular features has not been systematically compared to standard single-lesion tumor biopsies in prospective cohorts of patients. The use of plasma instead of tissue to guide therapy is particularly attractive for patients with small cell lung cancer (SCLC), a cancer whose aggressive clinical course making it exceedingly challenging to obtain tumor biopsies. MethodsHere, a prospective cohort of 49 plasma samples obtained before, during, and after treatment from 20 patients with recurrent SCLC, we study cfDNA low pass whole genome (0.1X coverage) and exome (130X) sequencing in comparison with time-point matched tumor, characterized using exome and transcriptome sequencing. ResultsDirect comparison of cfDNA versus tumor biopsy reveals that cfDNA not only mirrors the mutation and copy number landscape of the corresponding tumor but also identifies clinically relevant resistance mechanisms and cancer driver alterations not found in matched tumor biopsies. Longitudinal cfDNA analysis reliably tracks tumor response, progression, and clonal evolution. Genomic sequencing coverage of plasma DNA fragments around transcription start sites shows distinct treatment-related changes and captures the expression of key transcription factors such as NEUROD1 and REST in the corresponding SCLC tumors, allowing prediction of SCLC neuroendocrine phenotypes and treatment responses. Conclusions These findings have important implications for non-invasive stratification and subtype-specific therapies for patients with SCLC, now treated as a single disease.

cancer biology↗

bioRxiv2024

Protocols for circulating neutrophil depletion in neonatal C57/Bl6 mice

Murine neonatal neutrophil depletion strategies have problems achieving deep neutrophil clearance and accurate residual neutrophil fraction detection. An isotype switch method can achieve profound neutrophil clearance using a combination of anti-Ly6G and anti-rat {kappa} Ig light chain antibodies in adult C57Bl/6 mice, proven by extra- and intracellular Ly6G detection by flow cytometry. We adapted this technique to neonatal mice, testing four neutrophil depletion strategies in the peripheral circulation, bone marrow, and spleen. Four protocols were tested: P3 Ly6G and P1-3 Ly6G (anti-Ly6G on postnatal days (P) 3 and 1-3 respectively), and P3 Dual and P1-3 Dual (anti-Ly6G and anti-rat {kappa} Ig light chain on P3 and P1-3 respectively). Intracellular and extracellular Ly6G presence was detected using flow cytometry. Isotype control antibodies were used as controls. P1-3 Dual protocol achieved significantly better neutrophil depletion than the P1-3 Ly6G or P3 Ly6G protocols (97% vs. 74% and 97% vs. 50%, respectively) in the peripheral circulation. The P3 Dual protocol alone was enough to achieve significantly better neutrophil clearance (93%) than any of the Ly6G alone protocols. The Ly6G alone protocols led to near-total elimination of extracellular Ly6G. However, there was a significant presence of intracellular Ly6G in the CD45+ cell population, evading detection by extracellular Ly6G antibody-based detection methods. P3 protocols perform better than P1-3 protocols for bone marrow and splenic neutrophil clearance. Thus, the P3 Dual protocol might be the most effective and ethical protocol to induce profound neutrophil depletion in neonatal mice, an alternative to daily anti-Ly6G injections. Summary SentenceDual antibody-based neutrophil depletion effectively induces circulating neutrophil clearance in neonatal mice.

immunology↗

bioRxiv2024

Transient lagging chromosomes cause primary microcephaly

Primary microcephaly results from the impaired neuronal progenitor proliferation, causing reduced brain size and impaired cognitive abilities. Loss of the most frequently microcephaly genes, WDR62 and ASPM, slows down poleward microtubule flux and results in transient lagging chromosomes in anaphase. Whether these defects cause primary microcephaly is unknown. Here we show that transient lagging chromosomes elicit an Aurora-B-dependent activation of 53BP1 and p21, impairing cell proliferation. Co-depletion of the microtubule depolymerase inhibitor CAMSAP1/Patronin in a WDR62 depletion background, restores normal flux rates, suppresses lagging chromosomes, and allows normal cell proliferation in human cells, while rescuing the small brain and the cognitive defects in fly larvae. We postulate that transient lagging chromosomes in anaphase and 53BP1/p21-dependent response they elicit, are a major driver of primary microcephaly.

cell biology↗

bioRxiv2024

Activity based proteome profiling of serum serinehydrolases: application in pediatric abusive head trauma

PurposeTraumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial haemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes. Experimental designSerine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation and neuronal signaling. Here we investigated activity-based protein profiling (ABPP) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS). ResultsOur proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism. Conclusions and clinical relevanceTo our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.

neuroscience↗

bioRxiv2024

Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells. We demonstrated the prolonged survival of cell line-based and patient-derived multiple myeloma cells within our in vitro system and successfully flowed in donor-matched CAR-T cells. We then measured T cell survival, differentiation, and cytotoxicity against MM cells using a variety of analysis techniques. Our MM-on-a-chip system could elucidate the role of the BM microenvironment in MM survival and therapeutic evasion and inform the rational design of next-generation therapeutics. TEASERA multiple myeloma model can study why the disease is still challenging to treat despite options that work well in other cancers.

cancer biology↗

bioRxiv2024

Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology

Sex chromosomes are a fundamental aspect of sex-biased biology, but the extent to which homologous X-Y gene pairs ("the gametologs") contribute to sex-biased phenotypes remains hotly-debated. Although these genes exhibit large sex differences in expression throughout the body (XX females express both X members; XY males express one X and one Y member), there is conflicting evidence regarding the degree of functional divergence between the X and Y gametologs. Here, we use co-expression fingerprint (CF) analysis to characterize functional divergence between the X and Y members of 17 gametolog gene pairs across >40 human tissues. Gametologs exhibit functional divergence between the sexes that is driven by divergence between the X vs. Y gametologs (assayed in males) and is greatest among evolutionary distant gametolog pairs. These patterns reflect that X vs. Y gametologs show coordinated patterns of asymmetric coupling with large sets of autosomal genes, which are enriched for functional pathways and gene sets implicated in sex-biased biology and disease. These findings suggest that the X and Y gametologs have diverged in function, and prioritize specific gametolog pairs for future targeted experimental studies.

genomics↗