Histone lysine crotonylation (Kcr) is a post-translational modification of histone proteins that ... more Histone lysine crotonylation (Kcr) is a post-translational modification of histone proteins that is involved in the regulation of gene transcription, acute and chronic kidney injury, spermatogenesis, depression, cancer, and so forth. The identification of Kcr sites in proteins is important for characterizing and regulating primary biological mechanisms. The use of computational approaches such as machine learning and deep learning algorithms have emerged in recent years as the traditional wet-lab experiments are time-consuming and costly. We propose as part of this study a deep learning model based on a recurrent neural network (RNN) termed as Sohoko-Kcr for the prediction of Kcr sites. Through the embedded encoding of the peptide sequences, we investigate the efficiency of RNN-based models such as long short-term memory (LSTM), bidirectional LSTM (BiLSTM), and bidirectional gated recurrent unit (BiGRU) networks using cross-validation and independent tests. We also established the comparison between Sohoko-Kcr and other published tools to verify the efficiency of our model based on 3-fold, 5-fold, and 10-fold cross-validations using independent set tests. The results then show that the BiGRU model has consistently displayed outstanding performance and computational efficiency. Based on the proposed model, a webserver called Sohoko-Kcr was deployed for free use and is accessible at https://sohoko-research-9uu23.ondigitalocean.app.
Skeletal dysplasia is mainly caused by genetic mutations or endocrine abnormality. In this study,... more Skeletal dysplasia is mainly caused by genetic mutations or endocrine abnormality. In this study, a case of disproportionate dwarfism from the Iron Age Beishenjiaqiao cemetery in Xi'an, China is analyzed from the perspective of bioarchaeology. The individual shows disproportionately short stature, with reduced long-bone diaphyseal length especially of both humeri, unfused proximal humerus epiphyses, abnormal development of the shoulder and hip joints, left femoral head necrosis, and unusually gracile left femur and tibia shaft, demonstrating limited mobility and labor capacity. Hypothyroidism, pseudoachondroplasia, and multiple epiphyseal dysplasia are the most likely possible diagnoses although there are other possibilities. By combining the archaeological evidences and historical records, it is speculated that this individual lived a normal life and was well treated during her lifetime. Overall, this rare case concerning dwarfism not only enriches our knowledge of skeletal dysplasia among ancient Chinese in northern China but also demonstrates the humanitarian attitude of ancient society toward the disability.
Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and ... more Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpas by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 1612 individuals in 191 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this focused InDel panel is informative and polymorphic in Dingjie Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in Dingjie Sherpas. Descriptive findings from the PCA, ADMIXTURE, and TreeMix-based phylogenies suggested that studied Nepal Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Nepal Sherpas had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpas, core Tibetans, and Chokhopani formed one clade, which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from fineSTRUCTURE and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale genetic microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL and iHH12 showed natural selection signatures associated with disease susceptibility in Sherpas. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the InDel-based genotype data and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.
This research is intended to report on a case of healed foot amputation in Central Plains, China,... more This research is intended to report on a case of healed foot amputation in Central Plains, China, and to provide a differential diagnosis on the amputation. The material used is an adult skeleton, dating back to 8th–5th Centuries BCE, from Chongpingyuan site, Shaanxi, China. The methods used are macroscopic observations, microscope, and X-ray. Macroscopic observations indicated that the individual of interest was probably a male, around 50 to 70 years old, with a stature around 168.51 cm. Nearly one third of the distal end of his left tibia and fibula was absent, and the surface was remodeled with obvious signs of healing. Meanwhile, this individual suffered from osteoarthritis, lumbosacral transitional vertebrae, and several oral pathologies. Osteoarthritis was more profoundly found on the right limbs. Yue penalty (刖刑), which is often seen on scripts and artifacts in Bronze Age China, was an explanation for this amputation, while surgery amputation or traumatic incident cannot be entirely excluded. Contemporary images and artifacts of amputees suggested the usage of crutches. The social status and possibility of punitive amputation lead to the argument that this individual was unlikely to receive positive treatments after amputation. This study supplements the current research of ancient amputation in early China and provides an opportunity to look at the penal system and medical knowledge of the Zhou Dynasty. The absence of cutting marks left a questionable point with regards to the tools used for amputations.
Frontiers in Genetics: Evolutionary and Population Genetics, 2021
The evolutionary and admixture history of Han Chinese have been widely discussed via traditional ... more The evolutionary and admixture history of Han Chinese have been widely discussed via traditional autosomal and uniparental genetic markers [e.g., short tandem repeats, low-density single nucleotide polymorphisms). However, their fine-scale genetic landscapes (admixture scenarios and natural selection signatures) based on the high-density allele/haplotype sharing patterns have not been deeply characterized. Here, we collected and generated genome-wide data of 50 Han Chinese individuals from four populations in Guizhou Province, one of the most ethnolinguistically diverse regions, and merged it with over 3,000 publicly available modern and ancient Eurasians to describe the genetic origin and population admixture history of Guizhou Hans and their neighbors. PCA and ADMIXTURE results showed that the studied four populations were homogeneous and grouped closely to central East Asians. Genetic homogeneity within Guizhou populations was further confirmed via the observed strong genetic affinity with inland Hmong-Mien people through the observed genetic clade in Fst and outgroup f3/f4-statistics. qpGraph-based phylogenies and f4-based demographic models illuminated that Guizhou Hans were well fitted via the admixture of ancient Yellow River Millet farmers related to Lajia people and southern Yangtze River farmers related to Hanben people. Further ChromoPainter-based chromosome painting profiles and GLOBETROTTER-based admixture signatures confirmed the two best source matches for southwestern Hans, respectively, from northern Shaanxi Hans and southern indigenes with variable mixture proportions in the historical period. Further three-way admixture models revealed larger genetic contributions from coastal southern East Asians into Guizhou Hans compared with the proposed inland ancient source from mainland Southeast Asia. We also identified candidate loci (e.g., MTUS2, NOTCH4, EDAR, ADH1B, and ABCG2) with strong natural selection signatures in Guizhou Hans via iHS, nSL, and ihh, which were associated with the susceptibility of the multiple complex diseases, morphology formation, alcohol and lipid metabolism. Generally, we provided a case and ideal strategy to reconstruct the detailed demographic evolutionary history of Guizhou Hans, which provided new insights into the fine-scale genomic formation of one ethnolinguistically specific targeted population from the comprehensive perspectives of the shared unlinked alleles, linked haplotypes, and paternal and maternal lineages.
Frontiers in Genetics: section Evolutionary and Population Genetics, 2021
Archeologically attested human occupation on the Tibetan Plateau (TP) can be traced back to 160 t... more Archeologically attested human occupation on the Tibetan Plateau (TP) can be traced back to 160 thousand years ago (kya) via the archaic Xiahe people and 30∼40 kya via the Nwya Devu anatomically modern human. However, the history of the Tibetan populations and their migration inferred from the ancient and modern DNA remains unclear. Here, we performed the first ancient and modern genomic meta-analysis among 3,017 Paleolithic to present-day Eastern Eurasian genomes (2,444 modern individuals from 183 populations and 573 ancient individuals). We identified a close genetic connection between the ancient-modern highland Tibetans and lowland island/coastal Neolithic Northern East Asians (NEA). This observed genetic affinity reflected the primary ancestry of high-altitude Tibeto-Burman speakers originated from the Neolithic farming populations in the Yellow River Basin. The identified pattern was consistent with the proposed common north-China origin hypothesis of the Sino-Tibetan languages and dispersal patterns of the northern millet farmers. We also observed the genetic differentiation between the highlanders and lowland NEAs. The former harbored more deeply diverged Hoabinhian/Onge-related ancestry and the latter possessed more Neolithic southern East Asian (SEA) or Siberian-related ancestry. Our reconstructed qpAdm and qpGraph models suggested the co-existence of Paleolithic and Neolithic ancestries in the Neolithic to modern East Asian highlanders. Additionally, we found that Tibetans from Ü-Tsang/Ando/Kham regions showed a strong population stratification consistent with their cultural background and geographic terrain. Ü-Tsang Tibetans possessed a stronger Chokhopani-affinity, Ando Tibetans had more Western Eurasian related ancestry and Kham Tibetans harbored greater Neolithic southern EA ancestry. Generally, ancient and modern genomes documented multiple waves of human migrations in the TP’s past. The first layer of local hunter-gatherers mixed with incoming millet farmers and arose the Chokhopani-associated Proto-Tibetan-Burman highlanders, which further respectively mixed with additional genetic contributors from the western Eurasian Steppe, Yellow River and Yangtze River and finally gave rise to the modern Ando, Ü-Tsang and Kham Tibetans.
Bioarchaeological research provides unique insights on human adaptation, diet, lifestyle and epid... more Bioarchaeological research provides unique insights on human adaptation, diet, lifestyle and epidemiology. The Mogou Bioarchaeology Project explores how health was affected by the Bronze Age transition in north-west China. Preliminary results reveal that the inhabitants experienced substantial physiological stress, infectious disease and lethal trauma.
Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynam... more Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f3/f4 statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.
Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor si... more Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor significant allele frequency differences among diverse ethnic groups. The use of sets of AIMs to reconstruct population history and genetic relationships is attracting interest in the forensic community, because biogeographic ancestry information for a casework sample can potentially be predicted and used to guide the investigative process. However, subpopulation ancestry inference within East Asia remains in its infancy due to a lack of population reference data collection and incomplete validation work on newly developed or commercial AIM sets. In the present study, 316 Chinese persons, including 85 Sinitic-speaking Haikou Han, 120 Qiongzhong Hlai and 111 Daozhen Gelao individuals belonging to Tai-Kadai-speaking populations, were analyzed using the Precision ID Ancestry Panel (165 AISNPs). Combined with our previous 165-AISNP data (375 individuals from 6 populations), the 1000 Genomes Project and forensic literature, comprehensive population genetic comparisons and ancestry inference were further performed via ADMIXTURE, TreeMix, PCA, f-statistics and N-J tree. Although several nonpolymorphic loci were identified in the three southern Chinese populations, the forensic parameters of this ancestry inference panel were better than those for the 23 STR-based Huaxia Platinum System, which is suitable for use as a robust tool in forensic individual identification and parentage testing. The results based on the ancestry assignment and admixture proportion evaluation revealed that this panel could be used successfully to assign individuals at a continental scale but also possessed obvious limitations in discriminatory power in intercontinental individuals, especially for European-Asian admixed Uyghurs or in populations lacking reference databases. Population genetic analyses further revealed five continental population clusters and three East Asian-focused population subgroups, which is consistent with linguistic affiliations. Ancestry composition and multiple phylogenetic analysis further demonstrated that the geographically isolated Qiongzhong Hlai harbored a close phylogenetic relationship with Austronesian speakers and possessed a homogenous Tai-Kadai-dominant ancestry, which could be used as the ancestral source proxy in population history reconstruction of Tai-Kadai-speaking populations and as one of the representatives for forensic database establishment. In summary, more population-specific AIM sets focused on East Asian subpopulations, comprehensive algorithms and high-coverage population reference data should be developed and validated in the next step.
The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA... more The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet—where it forms approximately 84% of the gene pool in some groups—and to the Central Plain, where it has contributed around 59–84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai–Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.
The Han Chinese are the world's largest ethnic group residing across China. Shaanxi province in n... more The Han Chinese are the world's largest ethnic group residing across China. Shaanxi province in northern China was a pastoral–agricultural interlacing region sensitive to climate change since Neolithic times, which makes it a vital place for studying population dynamics. However, genetic studies of Shaanxi Han are underrepresented due to the lack of high-density sampling and genome-wide data. Here, we genotyped 700 000 single nucleotide polymorphisms (SNPs) in 200 Han individuals from nine populations in Shaanxi and compared with available modern and ancient Eurasian individuals. We revealed a north–south genetic cline in Han Chinese with Shaanxi Han locating at the northern side of the cline. We detected the western Eurasian-related admixture in Shaanxi populations, especially in Guanzhong and Shanbei Han Chinese in proportions of 2%–4.6%. Shaanxi Han were suggested to derive a large part of ancestry (39%–69%) from a lineage that also contributed largely to ancient and present-day Tibetans (85%) as well as southern Han, supporting the common northern China origin of modern Sino-Tibetan-speaking populations and southwestward expansion of millet farmers from the middle-upper Yellow River Basin to the Tibetan Plateau and to southern China. The rest of the ancestry of Shaanxi Han was from a lineage closely related to ancient and present-day Austronesian and Tai-Kadai speaking populations in southern China and Southeast Asia. We also observed a genetic substructure in Shaanxi Han in terms of north–south-related ancestry corresponding well to the latitudes. Maternal mitochondrial DNA and paternal Y-chromosome lineages further demonstrated the aforementioned admixture pattern of Han Chinese in Shaanxi province.
Archaeological, genetic and linguistic evidence supported that northern China is the original cen... more Archaeological, genetic and linguistic evidence supported that northern China is the original center of modern Sino‐Tibetan‐speaking populations. However, the demographic history of subsequent southward migration and genetic admixture of Han Chinese with surrounding indigenous populations keep uncharacterized, and the language shifts and assimilations accompanied by movement of people or just an adaptation of cultural ideas among populations in central China is still unclear, especially for Tibeto‐Burman‐speaking Tujia and central Han Chinese populations. To resolve this, we genotyped over 600K genome‐wide markers in 505 unrelated individuals from 63 indigenous populations. Our results showed both studied Han and Tujia were at the intermediate position in the modern East Asian north‐south genetic cline and there was a correlation between the genetic composition and the latitude. We observed the strong genetic assimilation between Tujia people and central Han Chinese, which suggested massive population movements and genetic admixture under language borrowing. Tujia and central Han Chinese could be modeled as a two‐way admixture deriving primary ancestry from a northern ancestral population closely related to the ancient DevilsCave and present‐day Tibetans and a southern ancestral population closely related to the present‐day Tai‐Kadai and Austronesian‐speaking groups. The ancestral northern population we suspect to be related to the Neolithic millet farming groups in the Yellow River Basin or central China. We showed newly genotyped populations in Hubei Province had a higher proportion of DevilsCave or modern Tungusic/Mongolic‐related northern ancestries, while the Hunan populations harbored a higher proportion of Austronesian/Tai‐Kadai‐related southern ancestries.
Human skeletal morphology is a dynamic system affected by both physiological and environmental fa... more Human skeletal morphology is a dynamic system affected by both physiological and environmental factors, due to the functional adaptation and remodeling responses of bones. To further explore the adaptation of bone to the environment and the consequent subsistence strategies determined by the diverse natural contexts in the Anthropocene, this study presents a comparative study on the tibiae of seven ancient populations located in different regions of East Asia. Through the analysis of the tibial shaft morphology, a comparative analysis between the populations and genders was conducted to evaluate the differences in external morphology and sexual division of labor. The cnemic indices of the tibial shaft were selected to quantify the external shape. Results showed that different populations had different tibial morphology. Among males, those of Jinggouzi had the flattest tibia while those of Changle had the widest tibia. Among the females, females of Hanben had the flattest tibia, whereas tibia from females of Shiqiao, Changle, and Yinxu were among the widest. The sexual dimorphism was relatively larger in Shiqiao and Jinggouzi and smaller in Tuchengzi and Changle. Through a combination of previous archaeological findings, historical records, and ethnography of the aboriginal Taiwanese, it is concluded that the terrain and ecological environments laid basis for varied subsistence strategies. In addition, the mobility and social labor division under a particular subsistence strategy further contributed to the adaptation of the lower limb morphology to its context. The comparative analysis provides further insight on habitual activities, terrestrial mobility patterns, and subsistence strategies of the populations, which lived in different environmental contexts during the Bronze Age and early Iron Age, thus demonstrating the diverse interactions between human populations and natural environment in the Anthropocene.
This study reports a paleopathological differential diagnosis on the skeleton from Shiyanzi Cemet... more This study reports a paleopathological differential diagnosis on the skeleton from Shiyanzi Cemetery site of Han Dynasty(2040 BP) in Ningxia. This specimen shows bone lesion on most part of the calvarium. Margins of lesion demonstrate scalloped borders with osteoblastic marginal uplift. The irregular and inward to outward-like beveled margins shows a possible neoplasm from the inside out. The combination of macroscopic observation and CT scanning provides more comprehensive information about ancient human disease and improves the credibility of diagnosis. According to the previous clinical reports, based on the morphology, distribution of the lesion, this individual may suffered from a severe metastatic carcinoma.
This study focuses on the knowledge of parasites, especially endoparasites, in the Ming Dynasty t... more This study focuses on the knowledge of parasites, especially endoparasites, in the Ming Dynasty through the combination of paleoparasitological records and the famous medical book, the Compendium of Materia Medica. This study summarizes the paleoparasitological findings in the Ming Dynasty and further discusses the causes, remedies, and cures in the Compendium of Materia Medica. With the knowledge of modern medicine, this study proposes possible causes of parasitic infections seen through the daily activities in the Ming Dynasty. Lastly, this study tries to explain the reasons behind the disparency in the records between paleoparasitological and written texts.
Chemometrics and Intelligent Laboratory Systems, 2020
Protein post-translational modification (PTM) is a process where proteins, after being created, a... more Protein post-translational modification (PTM) is a process where proteins, after being created, are modified through chemical processes in the body. Some recent studies have shown that PTM sites play an important role in signaling transduction, transcriptional regulation, and apoptosis. Among different types of PTM, the modification at Lysine (K) is the most frequently observed PTMs. Therefore, identifying Lysine PTM sites could be the key to decipher its mysterious structures and functions which are important in cell biology and diseases. Few studies have addressed this necessary problem using computational models; however, the predictive performance is not satisfactory. Thus, we aim to improve the performance results by using a novel combination with convolutional neural networks and sequence graph transform. The absolute-true rates within the cross-validation and independent achieved 85.21% and 85%, respectively. Compared to other methods as well as state-of-the-art published works, our proposed model reach performed better on a benchmark dataset. Our results show that we can propose an efficient model for improving the predictive performance of Lysine PTM sites. Moreover, it also suggests that deep learning and graph theory-based features could open a new avenue in biochemical modelling using sequence information.
Abstract
Objective
Paleopathological evidence of cancer from past populations is rare, especiall... more Abstract
Objective Paleopathological evidence of cancer from past populations is rare, especially outside of Europe and North Africa. This study expands upon the current temporal and spatial distribution of cancer by presenting a probable case of multiple myeloma from Bronze Age China.
Material The human skeletal remains of an adult male from the Qijia culture horizon (1750−1400 BCE) of the Bronze Age cemetery of Mogou (磨沟), located in Gansu Province, Northwest China.
Methods The human skeletal remains were assessed macroscopically and radiographically using plain x-rays.
Results Multiple ovoid-shaped osteolytic lesions with sharply demarcated margins were observed. The axial skeletal had the greatest involvement, specifically the vertebrae, ribs, and sternum. Radiographic imaging revealed more extensive destruction of cancellous than cortical bone, indicating that the marrow was the focal point of the disease.
Conclusion Based on the nature, distribution, and radiographic appearance of the lesions, the most likely diagnosis is multiple myeloma.
Significance This is one of the only cases of cancer identified in archaeological human skeletal remains from East Asia and is the first published case of a hematopoietic malignancy from mainland China. The analysis and publication of examples of neoplasia from areas that expand upon the current known temporal and spatial distribution is necessary in order to better reconstruct the history and evolution of cancer.
Limitations Poor skeletal preservation prevented the full extent of osteolytic lesions to be observed.
Suggestions for future research By placing case studies such as this into a temporal and spatial framework, it is possible for future research to begin to interrogate possible underlying causes of cancer in ancient populations within the context of changing environmental conditions and subsistence strategies.
Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by ... more Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.
Decapitation is an ancient practice in Asia with inadequate research. The present study reports o... more Decapitation is an ancient practice in Asia with inadequate research. The present study reports on the osteological examination of a headless skeleton excavated from a high-status tomb in Chu State style dating back to the late Warring States Period (ca. 3th century BC) in Lu’an, Anhui, China. The individual is identified as a victim of decapitation with five peri-mortem sharp force cut marks on the posterior parts of the cervical vertebrae, and another one on the right second metacarpal. Microscopic observation of the kerfs, the historical records and archaeological evidence support the speculation that the individual could be a warrior of Chu State, who is decapitated after being wounded during the war against the Qin State. The hacking implement and the sequences of the cut marks are further discussed to reconstruct the process of execution. This multidisciplinary reconstruction is the first scientific osteological analysis of the decapitation on the human remains from the Chinese Bronze Age. Moreover, it will enrich our knowledge of the decapitation phenomenon in terms of war and execution in ancient China.
Archaeological, genetic and linguistic evidence supported that northern China is the original cen... more Archaeological, genetic and linguistic evidence supported that northern China is the original center of modern Sino‐Tibetan‐speaking populations. However, the demographic history of subsequent southward migration and genetic admixture of Han Chinese with surrounding indigenous populations keep uncharacterized, and the language shifts and assimilations accompanied by movement of people or just an adaptation of cultural ideas among populations in central China is still unclear, especially for Tibeto‐Burman‐speaking Tujia and central Han Chinese populations. To resolve this, we genotyped over 600K genome‐wide markers in 505 unrelated individuals from 63 indigenous populations. Our results showed both studied Han and Tujia were at the intermediate position in the modern East Asian north‐south genetic cline and there was a correlation between the genetic composition and the latitude. We observed the strong genetic assimilation between Tujia people and central Han Chinese, which suggested massive population movements and genetic admixture under language borrowing. Tujia and central Han Chinese could be modeled as a two‐way admixture deriving primary ancestry from a northern ancestral population closely related to the ancient DevilsCave and present‐day Tibetans and a southern ancestral population closely related to the present‐day Tai‐Kadai and Austronesian‐speaking groups. The ancestral northern population we suspect to be related to the Neolithic millet farming groups in the Yellow River Basin or central China. We showed newly genotyped populations in Hubei Province had a higher proportion of DevilsCave or modern Tungusic/Mongolic‐related northern ancestries, while the Hunan populations harbored a higher proportion of Austronesian/Tai‐Kadai‐related southern ancestries.
Histone lysine crotonylation (Kcr) is a post-translational modification of histone proteins that ... more Histone lysine crotonylation (Kcr) is a post-translational modification of histone proteins that is involved in the regulation of gene transcription, acute and chronic kidney injury, spermatogenesis, depression, cancer, and so forth. The identification of Kcr sites in proteins is important for characterizing and regulating primary biological mechanisms. The use of computational approaches such as machine learning and deep learning algorithms have emerged in recent years as the traditional wet-lab experiments are time-consuming and costly. We propose as part of this study a deep learning model based on a recurrent neural network (RNN) termed as Sohoko-Kcr for the prediction of Kcr sites. Through the embedded encoding of the peptide sequences, we investigate the efficiency of RNN-based models such as long short-term memory (LSTM), bidirectional LSTM (BiLSTM), and bidirectional gated recurrent unit (BiGRU) networks using cross-validation and independent tests. We also established the comparison between Sohoko-Kcr and other published tools to verify the efficiency of our model based on 3-fold, 5-fold, and 10-fold cross-validations using independent set tests. The results then show that the BiGRU model has consistently displayed outstanding performance and computational efficiency. Based on the proposed model, a webserver called Sohoko-Kcr was deployed for free use and is accessible at https://sohoko-research-9uu23.ondigitalocean.app.
Skeletal dysplasia is mainly caused by genetic mutations or endocrine abnormality. In this study,... more Skeletal dysplasia is mainly caused by genetic mutations or endocrine abnormality. In this study, a case of disproportionate dwarfism from the Iron Age Beishenjiaqiao cemetery in Xi'an, China is analyzed from the perspective of bioarchaeology. The individual shows disproportionately short stature, with reduced long-bone diaphyseal length especially of both humeri, unfused proximal humerus epiphyses, abnormal development of the shoulder and hip joints, left femoral head necrosis, and unusually gracile left femur and tibia shaft, demonstrating limited mobility and labor capacity. Hypothyroidism, pseudoachondroplasia, and multiple epiphyseal dysplasia are the most likely possible diagnoses although there are other possibilities. By combining the archaeological evidences and historical records, it is speculated that this individual lived a normal life and was well treated during her lifetime. Overall, this rare case concerning dwarfism not only enriches our knowledge of skeletal dysplasia among ancient Chinese in northern China but also demonstrates the humanitarian attitude of ancient society toward the disability.
Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and ... more Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpas by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 1612 individuals in 191 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this focused InDel panel is informative and polymorphic in Dingjie Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in Dingjie Sherpas. Descriptive findings from the PCA, ADMIXTURE, and TreeMix-based phylogenies suggested that studied Nepal Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Nepal Sherpas had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpas, core Tibetans, and Chokhopani formed one clade, which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from fineSTRUCTURE and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale genetic microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL and iHH12 showed natural selection signatures associated with disease susceptibility in Sherpas. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the InDel-based genotype data and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.
This research is intended to report on a case of healed foot amputation in Central Plains, China,... more This research is intended to report on a case of healed foot amputation in Central Plains, China, and to provide a differential diagnosis on the amputation. The material used is an adult skeleton, dating back to 8th–5th Centuries BCE, from Chongpingyuan site, Shaanxi, China. The methods used are macroscopic observations, microscope, and X-ray. Macroscopic observations indicated that the individual of interest was probably a male, around 50 to 70 years old, with a stature around 168.51 cm. Nearly one third of the distal end of his left tibia and fibula was absent, and the surface was remodeled with obvious signs of healing. Meanwhile, this individual suffered from osteoarthritis, lumbosacral transitional vertebrae, and several oral pathologies. Osteoarthritis was more profoundly found on the right limbs. Yue penalty (刖刑), which is often seen on scripts and artifacts in Bronze Age China, was an explanation for this amputation, while surgery amputation or traumatic incident cannot be entirely excluded. Contemporary images and artifacts of amputees suggested the usage of crutches. The social status and possibility of punitive amputation lead to the argument that this individual was unlikely to receive positive treatments after amputation. This study supplements the current research of ancient amputation in early China and provides an opportunity to look at the penal system and medical knowledge of the Zhou Dynasty. The absence of cutting marks left a questionable point with regards to the tools used for amputations.
Frontiers in Genetics: Evolutionary and Population Genetics, 2021
The evolutionary and admixture history of Han Chinese have been widely discussed via traditional ... more The evolutionary and admixture history of Han Chinese have been widely discussed via traditional autosomal and uniparental genetic markers [e.g., short tandem repeats, low-density single nucleotide polymorphisms). However, their fine-scale genetic landscapes (admixture scenarios and natural selection signatures) based on the high-density allele/haplotype sharing patterns have not been deeply characterized. Here, we collected and generated genome-wide data of 50 Han Chinese individuals from four populations in Guizhou Province, one of the most ethnolinguistically diverse regions, and merged it with over 3,000 publicly available modern and ancient Eurasians to describe the genetic origin and population admixture history of Guizhou Hans and their neighbors. PCA and ADMIXTURE results showed that the studied four populations were homogeneous and grouped closely to central East Asians. Genetic homogeneity within Guizhou populations was further confirmed via the observed strong genetic affinity with inland Hmong-Mien people through the observed genetic clade in Fst and outgroup f3/f4-statistics. qpGraph-based phylogenies and f4-based demographic models illuminated that Guizhou Hans were well fitted via the admixture of ancient Yellow River Millet farmers related to Lajia people and southern Yangtze River farmers related to Hanben people. Further ChromoPainter-based chromosome painting profiles and GLOBETROTTER-based admixture signatures confirmed the two best source matches for southwestern Hans, respectively, from northern Shaanxi Hans and southern indigenes with variable mixture proportions in the historical period. Further three-way admixture models revealed larger genetic contributions from coastal southern East Asians into Guizhou Hans compared with the proposed inland ancient source from mainland Southeast Asia. We also identified candidate loci (e.g., MTUS2, NOTCH4, EDAR, ADH1B, and ABCG2) with strong natural selection signatures in Guizhou Hans via iHS, nSL, and ihh, which were associated with the susceptibility of the multiple complex diseases, morphology formation, alcohol and lipid metabolism. Generally, we provided a case and ideal strategy to reconstruct the detailed demographic evolutionary history of Guizhou Hans, which provided new insights into the fine-scale genomic formation of one ethnolinguistically specific targeted population from the comprehensive perspectives of the shared unlinked alleles, linked haplotypes, and paternal and maternal lineages.
Frontiers in Genetics: section Evolutionary and Population Genetics, 2021
Archeologically attested human occupation on the Tibetan Plateau (TP) can be traced back to 160 t... more Archeologically attested human occupation on the Tibetan Plateau (TP) can be traced back to 160 thousand years ago (kya) via the archaic Xiahe people and 30∼40 kya via the Nwya Devu anatomically modern human. However, the history of the Tibetan populations and their migration inferred from the ancient and modern DNA remains unclear. Here, we performed the first ancient and modern genomic meta-analysis among 3,017 Paleolithic to present-day Eastern Eurasian genomes (2,444 modern individuals from 183 populations and 573 ancient individuals). We identified a close genetic connection between the ancient-modern highland Tibetans and lowland island/coastal Neolithic Northern East Asians (NEA). This observed genetic affinity reflected the primary ancestry of high-altitude Tibeto-Burman speakers originated from the Neolithic farming populations in the Yellow River Basin. The identified pattern was consistent with the proposed common north-China origin hypothesis of the Sino-Tibetan languages and dispersal patterns of the northern millet farmers. We also observed the genetic differentiation between the highlanders and lowland NEAs. The former harbored more deeply diverged Hoabinhian/Onge-related ancestry and the latter possessed more Neolithic southern East Asian (SEA) or Siberian-related ancestry. Our reconstructed qpAdm and qpGraph models suggested the co-existence of Paleolithic and Neolithic ancestries in the Neolithic to modern East Asian highlanders. Additionally, we found that Tibetans from Ü-Tsang/Ando/Kham regions showed a strong population stratification consistent with their cultural background and geographic terrain. Ü-Tsang Tibetans possessed a stronger Chokhopani-affinity, Ando Tibetans had more Western Eurasian related ancestry and Kham Tibetans harbored greater Neolithic southern EA ancestry. Generally, ancient and modern genomes documented multiple waves of human migrations in the TP’s past. The first layer of local hunter-gatherers mixed with incoming millet farmers and arose the Chokhopani-associated Proto-Tibetan-Burman highlanders, which further respectively mixed with additional genetic contributors from the western Eurasian Steppe, Yellow River and Yangtze River and finally gave rise to the modern Ando, Ü-Tsang and Kham Tibetans.
Bioarchaeological research provides unique insights on human adaptation, diet, lifestyle and epid... more Bioarchaeological research provides unique insights on human adaptation, diet, lifestyle and epidemiology. The Mogou Bioarchaeology Project explores how health was affected by the Bronze Age transition in north-west China. Preliminary results reveal that the inhabitants experienced substantial physiological stress, infectious disease and lethal trauma.
Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynam... more Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f3/f4 statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.
Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor si... more Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor significant allele frequency differences among diverse ethnic groups. The use of sets of AIMs to reconstruct population history and genetic relationships is attracting interest in the forensic community, because biogeographic ancestry information for a casework sample can potentially be predicted and used to guide the investigative process. However, subpopulation ancestry inference within East Asia remains in its infancy due to a lack of population reference data collection and incomplete validation work on newly developed or commercial AIM sets. In the present study, 316 Chinese persons, including 85 Sinitic-speaking Haikou Han, 120 Qiongzhong Hlai and 111 Daozhen Gelao individuals belonging to Tai-Kadai-speaking populations, were analyzed using the Precision ID Ancestry Panel (165 AISNPs). Combined with our previous 165-AISNP data (375 individuals from 6 populations), the 1000 Genomes Project and forensic literature, comprehensive population genetic comparisons and ancestry inference were further performed via ADMIXTURE, TreeMix, PCA, f-statistics and N-J tree. Although several nonpolymorphic loci were identified in the three southern Chinese populations, the forensic parameters of this ancestry inference panel were better than those for the 23 STR-based Huaxia Platinum System, which is suitable for use as a robust tool in forensic individual identification and parentage testing. The results based on the ancestry assignment and admixture proportion evaluation revealed that this panel could be used successfully to assign individuals at a continental scale but also possessed obvious limitations in discriminatory power in intercontinental individuals, especially for European-Asian admixed Uyghurs or in populations lacking reference databases. Population genetic analyses further revealed five continental population clusters and three East Asian-focused population subgroups, which is consistent with linguistic affiliations. Ancestry composition and multiple phylogenetic analysis further demonstrated that the geographically isolated Qiongzhong Hlai harbored a close phylogenetic relationship with Austronesian speakers and possessed a homogenous Tai-Kadai-dominant ancestry, which could be used as the ancestral source proxy in population history reconstruction of Tai-Kadai-speaking populations and as one of the representatives for forensic database establishment. In summary, more population-specific AIM sets focused on East Asian subpopulations, comprehensive algorithms and high-coverage population reference data should be developed and validated in the next step.
The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA... more The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet—where it forms approximately 84% of the gene pool in some groups—and to the Central Plain, where it has contributed around 59–84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai–Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.
The Han Chinese are the world's largest ethnic group residing across China. Shaanxi province in n... more The Han Chinese are the world's largest ethnic group residing across China. Shaanxi province in northern China was a pastoral–agricultural interlacing region sensitive to climate change since Neolithic times, which makes it a vital place for studying population dynamics. However, genetic studies of Shaanxi Han are underrepresented due to the lack of high-density sampling and genome-wide data. Here, we genotyped 700 000 single nucleotide polymorphisms (SNPs) in 200 Han individuals from nine populations in Shaanxi and compared with available modern and ancient Eurasian individuals. We revealed a north–south genetic cline in Han Chinese with Shaanxi Han locating at the northern side of the cline. We detected the western Eurasian-related admixture in Shaanxi populations, especially in Guanzhong and Shanbei Han Chinese in proportions of 2%–4.6%. Shaanxi Han were suggested to derive a large part of ancestry (39%–69%) from a lineage that also contributed largely to ancient and present-day Tibetans (85%) as well as southern Han, supporting the common northern China origin of modern Sino-Tibetan-speaking populations and southwestward expansion of millet farmers from the middle-upper Yellow River Basin to the Tibetan Plateau and to southern China. The rest of the ancestry of Shaanxi Han was from a lineage closely related to ancient and present-day Austronesian and Tai-Kadai speaking populations in southern China and Southeast Asia. We also observed a genetic substructure in Shaanxi Han in terms of north–south-related ancestry corresponding well to the latitudes. Maternal mitochondrial DNA and paternal Y-chromosome lineages further demonstrated the aforementioned admixture pattern of Han Chinese in Shaanxi province.
Archaeological, genetic and linguistic evidence supported that northern China is the original cen... more Archaeological, genetic and linguistic evidence supported that northern China is the original center of modern Sino‐Tibetan‐speaking populations. However, the demographic history of subsequent southward migration and genetic admixture of Han Chinese with surrounding indigenous populations keep uncharacterized, and the language shifts and assimilations accompanied by movement of people or just an adaptation of cultural ideas among populations in central China is still unclear, especially for Tibeto‐Burman‐speaking Tujia and central Han Chinese populations. To resolve this, we genotyped over 600K genome‐wide markers in 505 unrelated individuals from 63 indigenous populations. Our results showed both studied Han and Tujia were at the intermediate position in the modern East Asian north‐south genetic cline and there was a correlation between the genetic composition and the latitude. We observed the strong genetic assimilation between Tujia people and central Han Chinese, which suggested massive population movements and genetic admixture under language borrowing. Tujia and central Han Chinese could be modeled as a two‐way admixture deriving primary ancestry from a northern ancestral population closely related to the ancient DevilsCave and present‐day Tibetans and a southern ancestral population closely related to the present‐day Tai‐Kadai and Austronesian‐speaking groups. The ancestral northern population we suspect to be related to the Neolithic millet farming groups in the Yellow River Basin or central China. We showed newly genotyped populations in Hubei Province had a higher proportion of DevilsCave or modern Tungusic/Mongolic‐related northern ancestries, while the Hunan populations harbored a higher proportion of Austronesian/Tai‐Kadai‐related southern ancestries.
Human skeletal morphology is a dynamic system affected by both physiological and environmental fa... more Human skeletal morphology is a dynamic system affected by both physiological and environmental factors, due to the functional adaptation and remodeling responses of bones. To further explore the adaptation of bone to the environment and the consequent subsistence strategies determined by the diverse natural contexts in the Anthropocene, this study presents a comparative study on the tibiae of seven ancient populations located in different regions of East Asia. Through the analysis of the tibial shaft morphology, a comparative analysis between the populations and genders was conducted to evaluate the differences in external morphology and sexual division of labor. The cnemic indices of the tibial shaft were selected to quantify the external shape. Results showed that different populations had different tibial morphology. Among males, those of Jinggouzi had the flattest tibia while those of Changle had the widest tibia. Among the females, females of Hanben had the flattest tibia, whereas tibia from females of Shiqiao, Changle, and Yinxu were among the widest. The sexual dimorphism was relatively larger in Shiqiao and Jinggouzi and smaller in Tuchengzi and Changle. Through a combination of previous archaeological findings, historical records, and ethnography of the aboriginal Taiwanese, it is concluded that the terrain and ecological environments laid basis for varied subsistence strategies. In addition, the mobility and social labor division under a particular subsistence strategy further contributed to the adaptation of the lower limb morphology to its context. The comparative analysis provides further insight on habitual activities, terrestrial mobility patterns, and subsistence strategies of the populations, which lived in different environmental contexts during the Bronze Age and early Iron Age, thus demonstrating the diverse interactions between human populations and natural environment in the Anthropocene.
This study reports a paleopathological differential diagnosis on the skeleton from Shiyanzi Cemet... more This study reports a paleopathological differential diagnosis on the skeleton from Shiyanzi Cemetery site of Han Dynasty(2040 BP) in Ningxia. This specimen shows bone lesion on most part of the calvarium. Margins of lesion demonstrate scalloped borders with osteoblastic marginal uplift. The irregular and inward to outward-like beveled margins shows a possible neoplasm from the inside out. The combination of macroscopic observation and CT scanning provides more comprehensive information about ancient human disease and improves the credibility of diagnosis. According to the previous clinical reports, based on the morphology, distribution of the lesion, this individual may suffered from a severe metastatic carcinoma.
This study focuses on the knowledge of parasites, especially endoparasites, in the Ming Dynasty t... more This study focuses on the knowledge of parasites, especially endoparasites, in the Ming Dynasty through the combination of paleoparasitological records and the famous medical book, the Compendium of Materia Medica. This study summarizes the paleoparasitological findings in the Ming Dynasty and further discusses the causes, remedies, and cures in the Compendium of Materia Medica. With the knowledge of modern medicine, this study proposes possible causes of parasitic infections seen through the daily activities in the Ming Dynasty. Lastly, this study tries to explain the reasons behind the disparency in the records between paleoparasitological and written texts.
Chemometrics and Intelligent Laboratory Systems, 2020
Protein post-translational modification (PTM) is a process where proteins, after being created, a... more Protein post-translational modification (PTM) is a process where proteins, after being created, are modified through chemical processes in the body. Some recent studies have shown that PTM sites play an important role in signaling transduction, transcriptional regulation, and apoptosis. Among different types of PTM, the modification at Lysine (K) is the most frequently observed PTMs. Therefore, identifying Lysine PTM sites could be the key to decipher its mysterious structures and functions which are important in cell biology and diseases. Few studies have addressed this necessary problem using computational models; however, the predictive performance is not satisfactory. Thus, we aim to improve the performance results by using a novel combination with convolutional neural networks and sequence graph transform. The absolute-true rates within the cross-validation and independent achieved 85.21% and 85%, respectively. Compared to other methods as well as state-of-the-art published works, our proposed model reach performed better on a benchmark dataset. Our results show that we can propose an efficient model for improving the predictive performance of Lysine PTM sites. Moreover, it also suggests that deep learning and graph theory-based features could open a new avenue in biochemical modelling using sequence information.
Abstract
Objective
Paleopathological evidence of cancer from past populations is rare, especiall... more Abstract
Objective Paleopathological evidence of cancer from past populations is rare, especially outside of Europe and North Africa. This study expands upon the current temporal and spatial distribution of cancer by presenting a probable case of multiple myeloma from Bronze Age China.
Material The human skeletal remains of an adult male from the Qijia culture horizon (1750−1400 BCE) of the Bronze Age cemetery of Mogou (磨沟), located in Gansu Province, Northwest China.
Methods The human skeletal remains were assessed macroscopically and radiographically using plain x-rays.
Results Multiple ovoid-shaped osteolytic lesions with sharply demarcated margins were observed. The axial skeletal had the greatest involvement, specifically the vertebrae, ribs, and sternum. Radiographic imaging revealed more extensive destruction of cancellous than cortical bone, indicating that the marrow was the focal point of the disease.
Conclusion Based on the nature, distribution, and radiographic appearance of the lesions, the most likely diagnosis is multiple myeloma.
Significance This is one of the only cases of cancer identified in archaeological human skeletal remains from East Asia and is the first published case of a hematopoietic malignancy from mainland China. The analysis and publication of examples of neoplasia from areas that expand upon the current known temporal and spatial distribution is necessary in order to better reconstruct the history and evolution of cancer.
Limitations Poor skeletal preservation prevented the full extent of osteolytic lesions to be observed.
Suggestions for future research By placing case studies such as this into a temporal and spatial framework, it is possible for future research to begin to interrogate possible underlying causes of cancer in ancient populations within the context of changing environmental conditions and subsistence strategies.
Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by ... more Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.
Decapitation is an ancient practice in Asia with inadequate research. The present study reports o... more Decapitation is an ancient practice in Asia with inadequate research. The present study reports on the osteological examination of a headless skeleton excavated from a high-status tomb in Chu State style dating back to the late Warring States Period (ca. 3th century BC) in Lu’an, Anhui, China. The individual is identified as a victim of decapitation with five peri-mortem sharp force cut marks on the posterior parts of the cervical vertebrae, and another one on the right second metacarpal. Microscopic observation of the kerfs, the historical records and archaeological evidence support the speculation that the individual could be a warrior of Chu State, who is decapitated after being wounded during the war against the Qin State. The hacking implement and the sequences of the cut marks are further discussed to reconstruct the process of execution. This multidisciplinary reconstruction is the first scientific osteological analysis of the decapitation on the human remains from the Chinese Bronze Age. Moreover, it will enrich our knowledge of the decapitation phenomenon in terms of war and execution in ancient China.
Archaeological, genetic and linguistic evidence supported that northern China is the original cen... more Archaeological, genetic and linguistic evidence supported that northern China is the original center of modern Sino‐Tibetan‐speaking populations. However, the demographic history of subsequent southward migration and genetic admixture of Han Chinese with surrounding indigenous populations keep uncharacterized, and the language shifts and assimilations accompanied by movement of people or just an adaptation of cultural ideas among populations in central China is still unclear, especially for Tibeto‐Burman‐speaking Tujia and central Han Chinese populations. To resolve this, we genotyped over 600K genome‐wide markers in 505 unrelated individuals from 63 indigenous populations. Our results showed both studied Han and Tujia were at the intermediate position in the modern East Asian north‐south genetic cline and there was a correlation between the genetic composition and the latitude. We observed the strong genetic assimilation between Tujia people and central Han Chinese, which suggested massive population movements and genetic admixture under language borrowing. Tujia and central Han Chinese could be modeled as a two‐way admixture deriving primary ancestry from a northern ancestral population closely related to the ancient DevilsCave and present‐day Tibetans and a southern ancestral population closely related to the present‐day Tai‐Kadai and Austronesian‐speaking groups. The ancestral northern population we suspect to be related to the Neolithic millet farming groups in the Yellow River Basin or central China. We showed newly genotyped populations in Hubei Province had a higher proportion of DevilsCave or modern Tungusic/Mongolic‐related northern ancestries, while the Hunan populations harbored a higher proportion of Austronesian/Tai‐Kadai‐related southern ancestries.
Hanben site is located at the south end of Yilan County in eastern Taiwan. This site is situated ... more Hanben site is located at the south end of Yilan County in eastern Taiwan. This site is situated on the coastline near the Pacific Ocean, only a few meters from the sea today. According to the current data, the site center is at 24°19'40 " north latitude and 121°45'56 " East longitude and about 19m above sea level. At least two prehistoric cultural layers in this site. Based on the ceramics and burial practices, the remains from L4 (1,600-1,200BP) could be considered to Shisanhang culture. The remains from L6 (2,000-1,650BP) cannot be identified with any exist prehistoric culture in eastern Taiwan. However, the flexed with sit position burial practice indeed shows some similarity with other prehistoric culture in eastern Taiwan. 20 specimens were taken from the site for collagen isotope analysis. Of the 20 specimens taken from the site, 10 were human, 4 were deer, 1 was pig and 5 were fish. The mean δ 13 C value for humans is-15.1‰, which is 5.8‰ higher than the herbivore (deer) value of-20.9‰. There is an estimated 0–2% increase between trophic levels in δ 13 C, strongly suggesting that herbivores were not the humans' only food source. Although herbivores were not the only food source of Hanben people, surprisingly in this work, human δ 13 C and δ 15 N values are notably lower than that of fish, which means that fish were also not the dominant dietary staple of Hanben people. The human values are, in fact, intermediate between herbivores and fish. Thus they are likely to have consumed a combination of foodstuffs. The result also indicates millet as one of the diet sources.
England’s most well known medieval kings because of his portrayal as a villain in Shakespeare’s p... more England’s most well known medieval kings because of his portrayal as a villain in Shakespeare’s play Richard III, in part a consequence of his usurping the throne and the perception of his spinal deformity. His body was buried in the church of the friars minor (Grey Friars) in Leicester.1 In September, 2012, Richard’s remains were excavated and sediment samples were taken from the sacral area of his pelvis, and control samples from his skull and the soil outside the grave cut (figure). Analysis was done with disaggregation with trisodium phosphate, microsieving with 300, 160, and 20 μm diameter mesh, and then light microscopy.2 The results showed the presence of multiple roundworm eggs (Ascaris lumbricoides) in the sacral sample, where the intestines would have been during life (figure). The eggs were decorticated and dimensions
Ecologies of Crusading, Colonization and Religious Conversion in the Medieval Baltic: Terra Sacra II., 2019
Detecting the intestinal parasites of past populations helps us not only to understand the diseas... more Detecting the intestinal parasites of past populations helps us not only to understand the diseases with which people suffered, but also the kinds of food they ate, they way they prepared their food, and the efficacy of their sanitation practices. It is clear that people living different lifestyles in different environments would have varied in their susceptibility to diseases in the past. Here we describe how we have analysed the faecal remains from inside a fourteenth century latrine from the city of Riga, and go on to interpret the results to improve our knowledge of the lives of the people who lived there. We then contrast our findings with those in other parts of Europe to show how the people of medieval Riga suffered significantly with fish tapeworm as a consequence of their cultural approach to food
Uploads
Publications by Ivy Yeh
Objective
Paleopathological evidence of cancer from past populations is rare, especially outside of Europe and North Africa. This study expands upon the current temporal and spatial distribution of cancer by presenting a probable case of multiple myeloma from Bronze Age China.
Material
The human skeletal remains of an adult male from the Qijia culture horizon (1750−1400 BCE) of the Bronze Age cemetery of Mogou (磨沟), located in Gansu Province, Northwest China.
Methods
The human skeletal remains were assessed macroscopically and radiographically using plain x-rays.
Results
Multiple ovoid-shaped osteolytic lesions with sharply demarcated margins were observed. The axial skeletal had the greatest involvement, specifically the vertebrae, ribs, and sternum. Radiographic imaging revealed more extensive destruction of cancellous than cortical bone, indicating that the marrow was the focal point of the disease.
Conclusion
Based on the nature, distribution, and radiographic appearance of the lesions, the most likely diagnosis is multiple myeloma.
Significance
This is one of the only cases of cancer identified in archaeological human skeletal remains from East Asia and is the first published case of a hematopoietic malignancy from mainland China. The analysis and publication of examples of neoplasia from areas that expand upon the current known temporal and spatial distribution is necessary in order to better reconstruct the history and evolution of cancer.
Limitations
Poor skeletal preservation prevented the full extent of osteolytic lesions to be observed.
Suggestions for future research
By placing case studies such as this into a temporal and spatial framework, it is possible for future research to begin to interrogate possible underlying causes of cancer in ancient populations within the context of changing environmental conditions and subsistence strategies.
Objective
Paleopathological evidence of cancer from past populations is rare, especially outside of Europe and North Africa. This study expands upon the current temporal and spatial distribution of cancer by presenting a probable case of multiple myeloma from Bronze Age China.
Material
The human skeletal remains of an adult male from the Qijia culture horizon (1750−1400 BCE) of the Bronze Age cemetery of Mogou (磨沟), located in Gansu Province, Northwest China.
Methods
The human skeletal remains were assessed macroscopically and radiographically using plain x-rays.
Results
Multiple ovoid-shaped osteolytic lesions with sharply demarcated margins were observed. The axial skeletal had the greatest involvement, specifically the vertebrae, ribs, and sternum. Radiographic imaging revealed more extensive destruction of cancellous than cortical bone, indicating that the marrow was the focal point of the disease.
Conclusion
Based on the nature, distribution, and radiographic appearance of the lesions, the most likely diagnosis is multiple myeloma.
Significance
This is one of the only cases of cancer identified in archaeological human skeletal remains from East Asia and is the first published case of a hematopoietic malignancy from mainland China. The analysis and publication of examples of neoplasia from areas that expand upon the current known temporal and spatial distribution is necessary in order to better reconstruct the history and evolution of cancer.
Limitations
Poor skeletal preservation prevented the full extent of osteolytic lesions to be observed.
Suggestions for future research
By placing case studies such as this into a temporal and spatial framework, it is possible for future research to begin to interrogate possible underlying causes of cancer in ancient populations within the context of changing environmental conditions and subsistence strategies.