Biology subjects

Sudoyo, H.

Publications and source records attributed to Sudoyo, H..

11 recordsLinked to original sources

bioRxiv2026

Rapid convergence toward an agriculturalist regulatory landscape following lifestyle transition in Bornean hunter-gatherers

The transition from hunter-gatherer to agricultural lifestyles is one of the landmarks in the history of human societies, but its phenotypic and immediate molecular consequences remain poorly understood. The Punan of Borneo clarify this question: two closely related groups -- the Punan Batu, still practising mobile foraging, and the Punan Tubu, resettled and farming within the last three generations -- share deep common ancestry and no detectable post-split gene flow from agricultural neighbours, allowing the molecular consequences of lifestyle change to be separated from underlying genetic architecture. We applied a multi-omics approach across these two groups and a neighbouring agriculturalist community, the Lundayeh, profiling whole-genome sequences, blood transcriptomes, and DNA methylation arrays. Despite their shared ancestry, the resettled Punan exhibit transcriptomic and methylation profiles more similar to the agriculturalists than to their still-foraging Punan relatives, with 87% fewer differentially expressed genes and substantially fewer differentially methylated sites in the Punan Tubu versus Lundayeh comparison, and show a 77% shift towards an agricultural state. Genes associated with fat metabolism and immune function are the main components of this molecular convergence. These findings demonstrate that lifestyle transition can reshape the human transcriptome and DNA methylation on timescales far shorter than genomic evolution, with implications for understanding the biological consequences of rapid subsistence change in Indigenous communities worldwide.

evolutionary biology↗

bioRxiv2026

Ancestral and environmental diversity shape the immune landscape in Indonesia

Island Southeast Asia (ISEA) remains consistently underrepresented in human genomic resources despite its exceptional ancestral and lifestyle diversity. The interplay between the regions complex population history and its environmental variation provide a window into how ancestry and environment jointly shape the human immune system. Here we report the generation of single-cell PBMC profiles from 199 Indonesians sampled across four communities in the islands of Bali and New Guinea. These groups capture diversity in regional genetic ancestries (East Asian-like and Papuan-like) and lifestyle contrasts (urban versus rural communities in Bali; highland versus lowland communities in New Guinea). We identify over 4,000 expression quantitative trait loci (eQTLs) across nine immune cell types, including eQTLs driven by introgression from both Neanderthals and Denisovans at genes such as IL7R, HLA-E, or STAT2. We also find evidence of local ancestry driving gene-by-environment interactions at pathogen receptors such as MARCO, although the majority of gene-by-environment interactions are not driven by differences in genetic structure between populations. Beyond direct genetic effects, we construct gene co-expression networks that consistently identify environmental signatures, as well as T-cell receptor repertoires that distinguish specific communities, with excess representation of interferon-stimulated genes in rural, but not urban samples. This work establishes a framework for population-aware functional genomics in understudied regions and highlights how ancestral and environmental diversity jointly shape human immunity in this globally important yet underrepresented region.

genomics↗

bioRxiv2025

From sporulation to village differentiation: the shaping of the social microbiome over rural-to-urban lifestyle transition in Indonesia

Despite established roles in human health and profound global diversity, existing gut microbiome datasets are biased toward Western urban cohorts, with especial under-representation of Southeast Asia. Here, we present a novel gut microbiome dataset from 116 Indonesians representing a cline from transitional hunter-gatherers to rural agricultural to urban lifestyles. We identify 1,304 species and 3,258 subspecies by assembling 11,070 metagenome-assembled genomes, revealing substantial species (15%) and subspecies level (50%) novelty. Novel taxa are rare, often village-specific, and depleted for sporulation genes, revealing a direct link between bacterial physiology, transmission, prevalence and discovery. We identify a rural-to-urban cline across multiple levels of biological organisation, from species abundance to microbiome composition and diversity. Furthermore, between-community, but not within-community, variation in diet is strongly predictive of microbiome composition, offering compelling evidence that microbiome divergence is driven by community-level differences. Our work highlights the interplay of host lifestyle, population structure and bacterial physiology in shaping microbiome diversity and biogeography, at the key scale of human communities.

microbiology↗

bioRxiv2024

The genetic origins and impacts of historical Papuan migrations into Wallacea

The tropical archipelago of Wallacea was first settled by anatomically modern humans (AMH) by 50 thousand years ago (kya), with descendent populations thought to have remained genetically isolated prior to the arrival of Austronesian seafarers around 3.5 kya. Modern Wallaceans exhibit a longitudinal countergradient of Papuan- and Asian-related ancestries widely considered as evidence for mixing between local populations and Austronesian seafarers, though converging multidisciplinary evidence suggests that the Papuan-related component instead comes primarily from back-migrations from New Guinea. Here, we reconstruct Wallacean population genetic history using more than 250 newly reported genomes from 12 Wallacean and three West Papuan populations and confirm that the vast majority of Papuan-related ancestry in Wallacea ([~]75-100%) comes from prehistoric migrations originating in New Guinea and only a minor fraction is attributable to the founding AMH settlers. Mixing between Papuan and local Wallacean lineages appear to have been confined to the western and central parts of the archipelago and likely occurred contemporaneously with the widespread introduction of genes from Austronesian seafarers--which now comprise between [~]40-85% of modern Wallacean ancestry--though dating historical admixture events remains challenging due to mixing continuing into the Historical Period. In conjunction with archaeological and linguistic records, our findings point to a dynamic Wallacean population history that was profoundly reshaped by the spread of Papuan genes, languages, and culture in the past 3,500 years.

evolutionary biology↗

bioRxiv2024

Benchmarking Imputed Low Coverage Genomes in a Human Population Genetics Context

Ongoing advances in population genomic methodologies have recently made it possible to study millions of loci across hundreds of genomes at a relatively low cost, by leveraging a combination of low-coverage shotgun sequencing and innovative genotype imputation methods. This approach has the potential to provide economical access to genotype information that is similar to most widely used low-cost genotyping approach - i.e. SNP panels - while avoiding potential issues related to loci being ascertained in distantly related populations. Nonetheless, adoption of imputation methods has been constrained by the lack of suitable reference panels of phased genomes, as performance degrades when panel individuals are distantly related to the target populations. Recent advances in imputation algorithms now allow genetic information from the target population to be used in the imputation process, however, potentially mitigating the lack of a suitable reference panel. Here we assess the performance of the recently released GLIMPSE imputation software on a set of 250 low coverage genomes ([~]3x) from populations from Island Southeast Asia and Near Oceania that are poorly represented in publicly available datasets, comparing the use of imputed genotypes against other common genotype calling methods for a range of standard population genomic analyses. We find that imputation performance and inference both greatly improved when genetic information from the 250 target individuals was leveraged, with comparable results to pseudo-haploid calls that trade off improved precision with reduced accuracy. Our study shows that imputed genotypes are a cost effective and robust basis for population genomic studies of groups, especially those that are poorly represented in publicly available data.

evolutionary biology↗

bioRxiv2024

Profiling genetically driven alternative splicing across the Indonesian Archipelago

One of the regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has contributed to human biology, especially in disease progression and the immune response. Nonetheless, this phenomenon remains poorly characterised across human populations, and it is unclear how genetic and environmental variation contribute to alternative splicing. Here, we examine a set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterizes Island Southeast Asia. We conduct a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using a hierarchical event-based statistical model, we detected over 1,000 significant differential AS events across all comparisons. Additionally, we identify over 6,000 genetic variants associated with changes in splicing (splicing quantitative trait loci; sQTLs), some of which are driven by Papuan-like genetic ancestry, and only show partial overlap with other publicly available sQTL datasets derived from other populations. Computational predictions of RNA binding activity revealed that a fraction of these sQTLs directly modulate the binding propensity of proteins involved in the splicing regulation of immune genes. Overall, these results contribute towards elucidating the role of genetic variation in shaping gene regulation in one of the most diverse regions in the world.

genomics↗

bioRxiv2022

The whole blood microbiome of Indonesians reveals that environmental differences shape immune gene expression signatures

Pathogens found within local environments are a major cause of morbidity and mortality. This is particularly true in Indonesia, where infectious diseases such as malaria or dengue are a significant part of the disease burden. Unequal investment in medical funding throughout Indonesia, particularly in rural areas, has resulted in under-reporting of cases, making surveillance challenging. Here, we use transcriptome data from 117 healthy individuals living on the islands of Mentawai, Sumba, and the Indonesian side of New Guinea Island to explore which pathogens are present within whole blood. We detect a range of taxa within RNA-sequencing data generated from whole blood and find that two pathogens--Flaviviridae and Plasmodium--are the most predominantly abundant, both of which are most pronounced in the easternmost island within our Indonesian dataset. We also compare the Indonesian data to two other cohorts from Mali and UK and find a distinct microbiome profile for each group. This study provides a framework for RNA-seq as a possible retrospective surveillance tool and an insight to what makes up the transient human blood microbiome.

genomics↗

bioRxiv2021

Transcriptomic profiles of Plasmodium falciparum and Plasmodium vivax-infected individuals in Indonesia

Malaria is one of the leading causes of illness and death globally. The vast majority of transcriptomic studies of the impact of malaria on human hosts have been conducted on populations of African ancestry suffering from Plasmodium falciparum infection, making it unclear whether biological responses observed in these studies can be generalised to other populations. Here, we perform differential expression analysis between healthy controls and malaria-infected patients within Indonesia, a country of over 260 million people which has substantial morbidity due to endemic malaria. We find that in samples infected with P. falciparum and P. vivax, there is an upregulation of genes involved in inflammation, the immediate early immune response, translation, and apoptosis. When comparing these findings to transcriptomic studies conducted in Africa (on P. falciparum) and South America (on P. vivax), we find that many pathways are shared. This is particularly apparent for receptor recognition and inflammation-related genes in P. falciparum and innate immune and chemokine-related genes in P. vivax infection. However, we also find that many genes are unique to the Indonesian population, particularly those involved in RNA processing, splicing, and cell surface receptor genes. This study provides a more comprehensive view of malaria infection outside of Africa and contributes to a better characterisation of malaria pathogenesis within humans across a range of genetic architectures.

genomics↗

bioRxiv2020

Genetic architecture of gene regulation in Indonesian populations identifies QTLs associated with local ancestry and archaic introgression

Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 participants across three island populations that capture the major sources of genomic diversity on the region. In a comparison with a European dataset, we identify 166 uniquely Indonesia-specific eQTLs, highlighting the benefits of performing association studies on non-European populations. By combining local ancestry and archaic introgression inference eQTLs and methylQTLs, we identify regulatory loci driven by modern Papuan ancestry as well as introgressed Denisovan and Neanderthal variation. GWAS colocalization connects QTLs detected here to hematological traits. Our findings illustrate how local ancestry and archaic introgression drive variation in gene regulation across genetically distinct and in admixed populations.

genomics↗

bioRxiv2020

Introgression, hominin dispersal and megafaunal survival in Late Pleistocene Island Southeast Asia

The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic super-archaic species - Homo luzonensis and H. floresiensis - were present around the time anatomically modern humans (AMH) arrived in the region >50,000 years ago. Contemporary human populations carry signals consistent with interbreeding events with Denisovans in ISEA - a species that is thought to be more closely related to AMH than the super-archaic endemic ISEA hominins. To query this disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes. Our results corroborate widespread Denisovan ancestry in ISEA populations but fail to detect any super-archaic admixture signals. By highlighting local megafaunal survival east of the Wallace Line as a potential signature of deep, pre-H. sapiens hominin-faunal interaction, we propose that this understudied region may hold the key to unlocking significant chapters in Denisovan prehistory.

evolutionary biology↗

bioRxiv2019

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago

Indonesia is the worlds fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10% of tested genes are differentially expressed between the islands of Mentawai (Sumatra) and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.7% of genes strongly correlating with nearby CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by very local environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.

genomics↗