Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness. Notably, the model maintains its robustness in low-coverage sequencing environments, demonstrating its potentials in clinical settings with limited sequencing resources. With its remarkable sensitivity and specificity, this approach promises to significantly improve the early diagnosis and management of ESCC. This study represents a substantial step forward in the application of cfDNA fragmentomics in cancer diagnostics, emphasizing the need for further research to fully establish its clinical efficacy.

Early detection of uterine corpus endometrial carcinoma utilizing plasma cfDNA fragmentomics.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics. METHODS: Peripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions. RESULTS: The cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier's outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%. CONCLUSION: This study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.

Mitogenomes of museum specimens provide new insight into species classification and recently reduced diversity of highly endangered Nomascus gibbons.

Our findings reveal that the western black crested gibbon (Nomascus concolor) did not divide into different subspecies, and the relatively low level of genetic diversity emphasizes the importance of monitoring this indicator for vulnerable wildlife. Meanwhile, phylogeographic analysis of the Nomascus genus shows a north-to-south trend of ancestral geographic distribution.

Ancient Mitogenomes Reveal the Maternal Genetic History of East Asian Dogs.

Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1 ka BP (1,000 years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4 ka BP, dramatically increasing after 3 ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins.

Overexpression of GmPAL Genes Enhances Soybean Resistance Against Heterodera glycines.

Soybean cyst nematode (Heterodera glycines, soybean cyst nematode [SCN]) disease adversely affects the yield of soybean and leads to billions of dollars in losses every year. To control the disease, it is necessary to study the resistance genes of the plant and their mechanisms. Isoflavonoids are secondary metabolites of the phenylalanine pathway, and they are synthesized in soybean. They are essential in plant response to biotic and abiotic stresses. In this study, we reported that phenylalanine ammonia-lyase (PAL) genes GmPALs involved in isoflavonoid biosynthesis, can positively regulate soybean resistance to SCN. Our previous study demonstrated that the expression of GmPAL genes in the resistant cultivar Huipizhi (HPZ) heidou are strongly induced by SCN. PAL is the rate-limiting enzyme that catalyzes the first step of phenylpropanoid metabolism, and it responds to biotic or abiotic stresses. Here, we demonstrate that the resistance of soybeans against SCN is suppressed by PAL inhibitor l-α-(aminooxy)-ß-phenylpropionic acid (L-AOPP) treatment. Overexpression of eight GmPAL genes caused diapause of nematodes in transgenic roots. In a petiole-feeding bioassay, we identified that two isoflavones, daidzein and genistein, could enhance resistance against SCN and suppress nematode development. This study thus reveals GmPAL-mediated resistance against SCN, information that has good application potential. The role of isoflavones in soybean resistance provides new information for the control of SCN. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Human genetic history on the Tibetan Plateau in the past 5100 years.

Using genome-wide data of 89 ancient individuals dated to 5100 to 100 years before the present (B.P.) from 29 sites across the Tibetan Plateau, we found plateau-specific ancestry across plateau populations, with substantial genetic structure indicating high differentiation before 2500 B.P. Northeastern plateau populations rapidly showed admixture associated with millet farmers by 4700 B.P. in the Gonghe Basin. High genetic similarity on the southern and southwestern plateau showed population expansion along the Yarlung Tsangpo River since 3400 years ago. Central and southeastern plateau populations revealed extensive genetic admixture within the plateau historically, with substantial ancestry related to that found in southern and southwestern plateau populations. Over the past ~700 years, substantial gene flow from lowland East Asia further shaped the genetic landscape of present-day plateau populations. The high-altitude adaptive EPAS1 allele was found in plateau populations as early as in a 5100-year-old individual and showed a sharp increase over the past 2800 years.

Maternal genetic history of ancient Tibetans over the past 4,000 years.

The settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity. Here, we reconstruct a 4,000-year maternal genetic history of Tibetans using 128 ancient mitochondrial genome data from 37 sites in Tibet. The phylogeny of haplotypes M9a1a, M9a1b, D4g2, G2a'c, and D4i show that ancient Tibetans shared the most recent common ancestor (TMRCA) with ancient Middle and Upper Yellow River populations around the Early and Middle Holocene. In addition, the connections between Tibetans and Northeastern Asians varied over the past 4,000 years, with a stronger matrilineal connection between the two during 4,000-3,000 BP, and a weakened connection after 3,000 BP, that were coincident with climate change, followed by a reinforced connection after the Tubo period (1,400-1,100 BP). Besides, an over 4,000-year matrilineal continuity was observed in some of the maternal lineages. We also found the maternal genetic structure of ancient Tibetans was correlated to the geography and interactions between ancient Tibetans and ancient Nepal and Pakistan populations. Overall, the maternal genetic history of Tibetans can be characterized as a long-term matrilineal continuity with frequent internal and external population interactions that were dynamically shaped by geography, climate changes, as well as historical events.

Ancient Mitogenomes Reveal the Origins and Genetic Structure of the Neolithic Shimao Population in Northern China.

Shimao City is considered an important political and religious center during the Late Neolithic Longshan period of the Middle Yellow River basin. The genetic history and population dynamics among the Shimao and other ancient populations, especially the Taosi-related populations, remain unknown. Here, we sequenced 172 complete mitochondrial genomes, ranging from the Yangshao to Longshan period, from individuals related to the Shimao culture in northern Shaanxi Province and Taosi culture in southern Shanxi Province, Middle Yellow River basin. Our results show that the populations inhabiting Shimao City had close genetic connections with an earlier population in the Middle Neolithic Yangshao period of northern Shaanxi Province, revealing a mostly local origin for the Shimao Society. In addition, among the populations in other regions of the Yellow River basin, the Shimao-related populations had the closest maternal affinity with the contemporaneous Taosi populations from the Longshan period. The Shimao-related populations also shared more affinity with present-day northern Han populations than with the minorities and southern Han in China. Our study provides a new perspective on the genetic origins and structure of the Shimao people and the population dynamics in the Middle Yellow River basin during the Neolithic period.

Bronze and Iron Age population movements underlie Xinjiang population history.

The Xinjiang region in northwest China is a historically important geographical passage between East and West Eurasia. By sequencing 201 ancient genomes from 39 archaeological sites, we clarify the complex demographic history of this region. Bronze Age Xinjiang populations are characterized by four major ancestries related to Early Bronze Age cultures from the central and eastern Steppe, Central Asian, and Tarim Basin regions. Admixtures between Middle and Late Bronze Age Steppe cultures continued during the Late Bronze and Iron Ages, along with an inflow of East and Central Asian ancestry. Historical era populations show similar admixed and diverse ancestries as those of present-day Xinjiang populations. These results document the influence that East and West Eurasian populations have had over time in the different regions of Xinjiang.

Ancient DNA reveals the maternal genetic history of East Asian domestic pigs.

Zoo-archaeological and genetic evidence suggest that pigs were domesticated independently in Central China and Eastern Anatolia along with the development of agricultural communities and civilizations. However, the genetic history of domestic pigs, especially in China, has not been fully explored. In this study, we generate 42 complete mitochondrial DNA sequences from ∼7500- to 2750-year-old individuals from the Yellow River basin. Our results show that the maternal genetic continuity of East Asian domestic pigs dates back to at least the Early to Middle Neolithic. In contrast, the Near Eastern ancestry in European domestic pigs saw a near-complete genomic replacement by the European wild boar. The majority of East Asian domestic pigs share close haplotypes, and the most recent common ancestor of most branches dates back to less than 20,000 years before present, inferred using new substitution rates of whole mitogenomes or combined protein-coding regions. Two major population expansion events of East Asian domestic pigs coincided with changes in climate, widespread adoption of introduced crops, and the development of agrarian societies. These findings add to our understanding of the maternal genetic composition and help to complete the picture of domestic pig evolutionary history in East Asia.

Fluorescent Soybean Hairy Root Construction and Its Application in the Soybean-Nematode Interaction: An Investigation.

BACKGROUND: The yield of soybean is limited by the soybean cyst nematode (SCN, Heterodera glycines). Soybean transformation plays a key role in gene function research but the stable genetic transformation of soybean usually takes half a year. METHODS: Here, we constructed a vector, pNI-GmUbi, in an Agrobacterium rhizogenes-mediated soybean hypocotyl transformation to induce fluorescent hairy roots (FHRs). RESULTS: We describe the operation of FHR-SCN, a fast, efficient and visual operation pathosystem to study the gene functions in the soybean-SCN interaction. With this method, FHRs were detected after 25 days in 4 cultivars (Williams 82, Zhonghuang 13, Huipizhiheidou and Peking) and at least 66.67% of the composite plants could be used to inoculate SCNs. The demographics of the SCN could be started 12 days post-SCN inoculation. Further, GmHS1pro-1 was overexpressed in the FHRs and GmHS1pro-1 provided an additional resistance in Williams 82. In addition, we found that jasmonic acid and JA-Ile increased in the transgenic soybean, implying that the resistance was mainly caused by affecting the content of JA and JA-Ile. CONCLUSIONS: In this study, we established a pathosystem, FHR-SCN, to verify the functional genes in soybeans and the SCN interaction. We also verified that GmHS1pro-1 provides additional resistance in both FHRs and transgenic soybeans, and the resistance may be caused by an increase in JA and JA-Ile contents.

Evaluation of Scopoletin from Penicillium janthinellum Snef1650 for the Control of Heterodera glycines in Soybean.

Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) is responsible for causing a major soybean disease globally. The fungal strain Penicillium janthinellum Snef1650 was evaluated against H. glycines. However, the effective determinants of the P. janthinellum strain are unknown. By performing pot experiments, a functioning compound was isolated from P. janthinellum Snef1650 through organic solvent extraction, semi-preparative HPLC, Sephadex LH-20 column chromatography, and silica gel column chromatography, and the isolated compound was identified to be scopoletin through 1H NMR, 13C NMR, and HPLC-MS. The pot experiments indicated that the treatment of soybean seeds with scopoletin drastically reduced the SCN population. The field experiments performed in 2017 and 2018 revealed that scopoletin decreased over 43.7% juveniles in the roots and over 61.55% cysts in the soil. Scopoletin treatment also promoted soybean growth and improved its yield, with an increase in plot yield by >5.33%. Scopoletin obtained from P. janthinellum Snef1650 could be used as an anti-H. glycines biocontrol agent.

The genomic origins of the Bronze Age Tarim Basin mummies.

The identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000-2800 BC from the Dzungarian Basin and 13 individuals dating to around 2100-1700 BC from the Tarim Basin, representing the earliest yet discovered human remains from North and South Xinjiang, respectively. We find that the Early Bronze Age Dzungarian individuals exhibit a predominantly Afanasievo ancestry with an additional local contribution, and the Early-Middle Bronze Age Tarim individuals contain only a local ancestry. The Tarim individuals from the site of Xiaohe further exhibit strong evidence of milk proteins in their dental calculus, indicating a reliance on dairy pastoralism at the site since its founding. Our results do not support previous hypotheses for the origin of the Tarim mummies, who were argued to be Proto-Tocharian-speaking pastoralists descended from the Afanasievo1,2 or to have originated among the Bactria-Margiana Archaeological Complex3 or Inner Asian Mountain Corridor cultures4. Instead, although Tocharian may have been plausibly introduced to the Dzungarian Basin by Afanasievo migrants during the Early Bronze Age, we find that the earliest Tarim Basin cultures appear to have arisen from a genetically isolated local population that adopted neighbouring pastoralist and agriculturalist practices, which allowed them to settle and thrive along the shifting riverine oases of the Taklamakan Desert.

Maternal genetic history of southern East Asians over the past 12,000 years.

Southern East Asia, including Guangxi and Fujian provinces in China, is home to diverse ethnic groups, languages, and cultures. Previous studies suggest a high complexity regarding population dynamics and the history of southern East Asians. However, large-scale genetic studies on ancient populations in this region are hindered by limited sample preservation. Here, using highly efficient DNA capture techniques, we obtain 48 complete mitochondrial genomes of individuals from Guangxi and Fujian in China and reconstruct their maternal genetic history over the past 12,000 years. We find a strong connection between southern East Asians dating to ~12,000-6000 years ago and present-day Southeast Asians. In addition, stronger genetic affinities to northern East Asians are observed in historical southern East Asians than Neolithic southern East Asians, suggesting increased interactions between northern and southern East Asians over time. Overall, we reveal dynamic connections between ancient southern East Asians and populations located in surrounding regions, as well as a shift in maternal genetic structure within the populations over time.

Genetic Continuity of Bronze Age Ancestry with Increased Steppe-Related Ancestry in Late Iron Age Uzbekistan.

Although Uzbekistan and Central Asia are known for the well-studied Bronze Age civilization of the Bactria-Margiana Archaeological Complex (BMAC), the lesser-known Iron Age was also a dynamic period that resulted in increased interaction and admixture among different cultures from this region. To broaden our understanding of events that impacted the demography and population structure of this region, we generated 27 genome-wide single-nucleotide polymorphism capture data sets of Late Iron Age individuals around the Historical Kushan time period (∼2100-1500 BP) from three sites in South Uzbekistan. Overall, Bronze Age ancestry persists into the Iron Age in Uzbekistan, with no major replacements of populations with Steppe-related ancestry. However, these individuals suggest diverse ancestries related to Iranian farmers, Anatolian farmers, and Steppe herders, with a small amount of West European Hunter Gatherer, East Asian, and South Asian Hunter Gatherer ancestry as well. Genetic affinity toward the Late Bronze Age Steppe herders and a higher Steppe-related ancestry than that found in BMAC populations suggest an increased mobility and interaction of individuals from the Northern Steppe in a Southward direction. In addition, a decrease of Iranian and an increase of Anatolian farmer-like ancestry in Uzbekistan Iron Age individuals were observed compared with the BMAC populations from Uzbekistan. Thus, despite continuity from the Bronze Age, increased admixture played a major role in the shift from the Bronze to the Iron Age in southern Uzbekistan. This mixed ancestry is also observed in other parts of the Steppe and Central Asia, suggesting more widespread admixture among local populations.