Australian Institute of Tropical Health and Medicine

Multi-omics in combination with advanced computational methodologies synthesizes diverse omics data to provide deeper insights into molecular interactions and offers transformative potential for unravelling phenomenon behind disease complexities, improving diagnostics, disease prevention, and personalized treatments. This integrative strategy enables our understanding of gene-environment relationships, chronic disease progression, and the intricate molecular pathways involved in health. Effective multi-omics analyses require robust data sharing, accessibility, interoperability, and governance, which are critical for linking genomic elements to phenotypic traits. The Global Alliance for Genomics and Health advocates for responsible data-sharing practices, by promoting key principles such as transparency and equity. By emphasizing a collaborative approach to data utilization, our proposed framework seeks to advance improved disease prevention and treatment strategies. Multi-disciplinary collaboration, encompassing researchers, clinicians, policy makers, and patient representatives, is pivotal for driving innovation and addressing rare disease diagnostics. The success of multi-omics applications hinges on the establishment of comprehensive datasets, understanding the functional implications of multi-omic variation, adherence to findable, accessible, interoperable, reusable (FAIR) and Collective Benefit, Authority to Control, Responsibility, and Ethics (CARE) principles, and the strengthening of global genomic commons, benefiting scientific research, drug development, and broader health initiatives. Our review highlights essential components of multi-omics integration, underscoring its potential to transform the landscape of precision medicine and improved patient outcomes worldwide.

To measure disability and frailty and assess measurement properties of the HIV Disability Questionnaire (HDQ) in outer regional Australian people living with human immunodeficiency virus (HIV). This cross-sectional, validity and reliability study included community-dwelling outer regional Australian adults with HIV. Participants completed the self-reported World Health Organization Disability Assessment Schedule 2.0 (WHODAS; scored 0-100), 5-Question Frail Scale (scored 0-5) and HDQ (scored 0-100). Median scores (Q1, Q3) for disability (WHODAS) and frailty (Frail Scale) were reported. HDQ validity was tested based on 16 a priori hypothesized relationships between WHODAS, Frail Scale and HDQ scores (threshold ≥75% confirmed), and HDQ internal consistency with Cronbach's alpha (acceptability threshold ≥ 0.70). Seven days after the initial completion, the HDQ was re-administered for test-retest reliability (intraclass correlation coefficient, acceptability threshold ≥ 0.75). Fifty participants were recruited, with a median age 55. Eighty-eight percent were male, and 38 participants completed the second HDQ. The median (Q1, Q3) scores were: WHODAS 9 (3,17), with domain scores ranging from 0 to 56. Pre-frailty (score 1-2) and Frailty (score 3-5) were present in 27% and 13% of participants, respectively. The HDQ demonstrated construct validity (81% hypotheses confirmed), internal consistency (Cronbach's alpha ≥ 0.79), except in the Episodic scale-Social inclusion domain (alpha = 0.34), and good test-retest reliability for all Presence and Severity domains (ICC range: 0.77-0.94). Disability, frailty and pre-frailty exist in this sample of outer regional Australians living with HIV. The HDQ showed acceptable construct validity, internal consistency and test-retest reliability to measure disability in this population. Australian New Zealand Clinical Trials Registry (ACTRN12623000090617).

Alternative splicing drives molecular diversity, yet livestock spliceopathies remain underrecognised despite their major economic impact. By synthesising evidence across major livestock species, we reveal how splicing defects disrupt production through recurrent patterns: splice variants in dosage-sensitive genes affect growth and fertility, breed-specific splice-regulatory changes drive disease susceptibility, and epigenetic modifications enable environmental adaptation. These patterns reflect evolutionary constraints and domestication pressures driving aberrant splicing in modern breeds. Recent technological advances enable systematic investigation and treatment: long-read sequencing uncovers hidden splicing complexity, while clustered regularly interspaced short palindromic repeats (CRISPR) and antisense oligonucleotides offer precision interventions. However, critical gaps persist in functional validation and population-scale mapping. Addressing these within the One Health framework will advance animal welfare, food security, and comparative medicine, positioning alternative splicing as a fundamental driver of phenotypic diversity.

BackgroundTo combat hepatocellular carcinoma (HCC) disease heterogeneity and growing mortality, there is an urgent need for targeted and personalized therapeutics. While syngeneic mouse models are commonly used for preclinical validation of these therapeutics, the lack of genetically characterized murine cell lines adds uncertainty to the study of drug‐gene interactions in these models. We previously generated a novel murine cell line, A52, from a diethylnitrosamine (DEN)‐induced adiponectin‐knockout mouse model. Here, we present a comprehensive genomic and transcriptomic characterization of the A52 cell line.MethodsA52 cells were grown in various culture medium compositions to investigate robustness to simple media. Whole‐genome sequencing (WGS) and RNAseq were performed on A52 cells from both cell culture and syngeneic tumor tissue, as well as a reference cell line representing non‐tumor cells, AML‐12.ResultsA52 was found to show robust growth in all medium compositions. Substantial chromosomal instability was observed in A52, including trisomy 15 and notable amplifications of oncogenic loci such as Myc and Cd274 (PDL‐1), alongside frequent small variants and structural rearrangements. Notably, the cell line harbors the common HCC driver Braf V584E mutation, and a novel Plk1 p.R364W variant predicted as a driver mutation. Transcriptomic profiling defined a distinct “A52 gene signature” enriched in EGFR‐ERBB signaling and cell migration pathways. Integrative analyses demonstrated that the A52 gene signature aligns closely with a subset of human HCC lacking CTNNB1 mutations.ConclusionThis study provides a critical genetic resource, facilitating more precise preclinical modeling and therapeutic validation in HCC.

Abstract Temperature fluctuations across space and time create a multidimensional thermal landscape within which organisms are exposed to local climates while conducting their daily activities. Tropical species are considered to be particularly sensitive to climate change, with narrow thermal safety margins - the buffer between operative and lethal temperatures. In tropical rainforests, however, species can hypothetically mediate thermal exposure via activity over two local thermal dimensions: vertical (ground-canopy) and temporal (day-night). Such spatiotemporal flexibility could protect species from elevated temperatures and improve thermal safety margins, but this mechanism has not been previously investigated. We test this hypothesis using rainforest ants at a warm lowland and cool upland site (100, 1200 m a.s.l.) in the Australian Wet Tropics. At lowland and upland sites, we quantified microclimate, foraging activity, community composition, and thermal ecology of ants across vertical and temporal dimensions. To assess spatiotemporal flexibility as a climate change mitigation strategy, we calculated thermal safety margins (TSM) as the difference between a species upper thermal limit (CT max ) and mean activity temperature (T e ). For each species in each of their spatiotemporal niches (ground-arboreal-day-night) we test whether shifting activity to cooler niches increases TSM using the hottest niches (arboreal and/or daytime) as a baseline. At both lowland and upland sites, ant species were highly stratified vertically, but the large majority (77 - 87.5%) were active both day and night, indicating widespread temporal generalisation. Shifting activity to cooler parts of the thermal landscape substantially improved TSMs: in the lowlands, species with arboreal diurnal foraging increased their TSM by an average of 4.4 °C (± 1.7 SE) by shifting to the ground and 6.7 °C (± 1.63 SE) by shifting to nocturnal foraging. Improvements were more modest in the uplands: arboreal diurnal foragers increased TSM by 2.1 °C (± 2.07 SE) and 2 °C (± 0.28 SE) for ground and nocturnal shifts respectively. We therefore demonstrate that foraging niche flexibility is an important climate-change mitigation trait and is most beneficial in the lowlands. Lowland diurnal canopy specialists, however, are most at risk. This represents a large proportion of tropical rainforest biodiversity, supporting previous hypotheses of lowland biotic attrition under climate change.

Abstract Mutvei's solution is a widely utilized standard staining method for revealing growth increments in biogenic carbonates; however, it is a slightly toxic, destructive approach with varying success across species groups. Therefore, there has been growing interest in finding non‐toxic, less destructive, and straightforward alternative techniques for studying growth structures, primarily focusing on long‐lived shells. This research focuses on an intertidal short‐lived marine gastropod— Conomurex luhuanus , collected from the Great Barrier Reef and a nearby archaeological site. A comparative analysis of common and cost‐effective tools used for growth increment visualization—including transmitted‐light microscopy, reflected‐light microscopy, cathodoluminescence, Raman spectroscopy, and acetate peel against Mutvei's solution—was undertaken to determine the most effective method to visualize daily growth increments in C. luhuanus . Overall, our results suggested that the relative patterns of measuring growth increments using all techniques are broadly consistent ( r = 0.4–0.7, p < 0.05) in the absence of slowed or halted growth. However, transmitted‐light microscopy (TML) was the only method that revealed more growth increments in an area where growth lines were too thin to be detected using other techniques, making it impossible to distinguish the daily growth increments using those techniques. Transmitted‐light microscopy, without staining or thin‐sectioning, was an effective and time‐efficient technique for visualizing daily growth increments in C. luhuanus . We suggest that TML can be considered as a preliminary step to investigate growth increments in other species before applying established approaches, such as Mutvei's solution.

Lates calcarifer, commonly known as barramundi perch, Asian sea bass or barramundi, is a significant aquaculture species across the Indo-Pacific. Barramundi typically exhibit a silver to bronze wild-type (WT) skin colour, with occasional golden (xanthic) variants of commercial interest. Although previous studies have identified gene expression differences between golden and WT variants, the genetic mechanism driving golden colouration remains elusive. By combining whole-genome enzymatic methylation sequencing (WGEMS) and RNA sequencing (RNA-seq), this study explores the molecular underpinnings of skin pigmentation within golden barramundi in an integrated approach. A total of 435 differentially methylated regions (DMR) were identified. Among 389 genes examined, an inverse relationship between expression ratio and promoter methylation levels was observed in 145 genes, suggesting a regulatory role of DNA methylation in gene expression. Notably, significant correlations between the changes in methylation and expression levels were identified in key pigment genes such as tyrp1 and pax7a, as well as potassium transmembrane transporter genes kir6.1 and kcnj3a. This suggests that barramundi colouration may result from complex molecular changes rather than the influence of a single or few genes. To further validate these observations, independent reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis was performed on representative genes, supporting the methylation-expression trends observed. This study is the first to characterize the whole-genome methylation landscape in barramundi, and one of the few to examine integrated methylome and transcriptome changes associated with pigmentation in teleost fish. By shedding light on the potential epigenetic mechanisms influencing rare skin colouration, this research contributes to the broader understanding of methylation-driven phenotypic variation in vertebrates and provides a foundation for future studies exploring environmental and developmental regulation of DNA methylation.

Widespread climate-driven increases in background tree mortality rates have the potential to reduce the carbon storage of terrestrial ecosystems, challenging their effectiveness as natural buffers against atmospheric CO2 enrichment with major consequences for the global carbon budget. However, the global extent of trends in tree mortality and their drivers remains poorly quantified. The Australian continent experiences one of the most variable climates on Earth and is host to a diverse range of forest biomes that have evolved high resistance to disturbance, providing a valuable test case for the pervasiveness of tree mortality trends. Here we compile an 83-year tree dynamics database (1941-2023) from >2,700 forest plots across Australia covering tropical savanna and rainforest and warm and cool temperate forests, to explore spatiotemporal patterns of tree mortality and the associated drivers. Over the past eight decades, we found a consistent trend of increasing tree mortality across the four forest biomes. This temporal trend persisted after accounting for stand structure and was exacerbated in forests with low moisture index or a high competition index. Species with traits associated with high growth rate-low wood density, high specific leaf area and short maximum height-exhibited higher average mortality, but the rate of mortality increase was comparable across different functional groups. Increasing mortality was not associated with increasing growth, given that stand basal area increments either declined or remained unchanged over time, but it was associated with increasing temperature over time. Our findings suggest that ongoing climate change has driven pervasive shifts in forest dynamics beyond natural recovery in a range of forest biomes with high resilience to disturbance, threatening the enduring capacity of forests to sequester carbon under current and future climate scenarios.

ABSTRACTBackgroundAntimicrobial resistance (AMR) is a critical global health concern, closely linked to the excessive and unregulated use of antimicrobials in livestock production systems, particularly in poultry farming. In Bangladesh, where poultry serves as a key source of animal protein, the misuse of antimicrobials contributes to the rapid emergence and spread of AMR, endangering animal, environmental and human health. Poultry farmers play a vital role in mitigating AMR through responsible antimicrobial usage (AMU), underscoring the urgent need for targeted educational interventions and strengthened regulatory frameworks to promote prudent AMU practices.MethodsThis cross‐sectional study assessed the knowledge, attitudes and practices (KAP) of poultry farmers regarding AMU across three districts in Bangladesh: Bogura, Rajshahi and Munshiganj. Data were collected from 294 poultry farmers through face‐to‐face interviews using a structured, pre‐validated questionnaire. KAP was classified using descriptive statistics and the chi‐square tests (p < 0.05).ResultsA majority of farmers (98.64%) reported us antimicrobials; however, only 50.34% obtained veterinary prescriptions. In addition, 73.13% were unaware of authorized prescribers, and 91.16% had no prior knowledge of AMR. Antimicrobials were frequently used during the brooding phase (61.90%) and as growth promoters (39.46%). A significant proportion of farmers (65.31%) believed antimicrobials could be used without veterinary advice, and 80.61% held misconceptions about their efficacy against viral infections. Furthermore, about 48.98% purchased these antimicrobials from local pharmacies without prior consultation with a veterinarian. The most commonly used antimicrobials were ciprofloxacin (58.84%), levofloxacin (43.20%), colistin (39.12%), amoxicillin (36.39%), doxycycline (36.39%) and tylosin (30.95%).ConclusionsThe widespread lack of knowledge and inappropriate attitudes toward AMU among poultry farmers is a significant driver of AMR. Addressing this issue necessitates comprehensive educational programs to enhance awareness, stricter enforcement of veterinary regulations to ensure responsible antimicrobial use and the establishment of robust AMU surveillance systems for continuous monitoring and assessment.