Whole Genome Analysis of the Red-Crowned Crane Provides Insight into Avian Longevity

The red-crowned crane (Grus japonensis) is an endangered, large-bodied crane native to East Asia. It is a traditional symbol of longevity and its long lifespan has been confirmed both in captivity and in the wild. Lifespan in birds is known to be positively correlated with body size and negatively correlated with metabolic rate, though the genetic mechanisms for the red-crowned crane's long lifespan have not previously been investigated. Using whole genome sequencing and comparative evolutionary analyses against the grey-crowned crane and other avian genomes, including the long-lived common ostrich, we identified red-crowned crane candidate genes with known associations with longevity. Among these are positively selected genes in metabolism and immunity pathways (NDUFA5, NDUFA8, NUDT12, SOD3, CTH, RPA1, PHAX, HNMT, HS2ST1, PPCDC, PSTK CD8B, GP9, IL-9R, and PTPRC). Our analyses provide genetic evidence for low metabolic rate and longevity, accompanied by possible convergent adaptation signatures among distantly related large and long-lived birds. Finally, we identified low genetic diversity in the red-crowned crane, consistent with its listing as an endangered species, and this genome should provide a useful genetic resource for future conservation studies of this rare and iconic species

Chromosome-scale assembly comparison of the Korean Reference Genome KOREF from PromethION and PacBio with Hi-C mapping information.

BACKGROUND:Long DNA reads produced by single-molecule and pore-based sequencers are more suitable for assembly and structural variation discovery than short-read DNA fragments. For de novo assembly, Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are the favorite options. However, PacBio's SMRT sequencing is expensive for a full human genome assembly and costs more than $40,000 US for 30× coverage as of 2019. ONT PromethION sequencing, on the other hand, is 1/12 the price of PacBio for the same coverage. This study aimed to compare the cost-effectiveness of ONT PromethION and PacBio's SMRT sequencing in relation to the quality. FINDINGS:We performed whole-genome de novo assemblies and comparison to construct an improved version of KOREF, the Korean reference genome, using sequencing data produced by PromethION and PacBio. With PromethION, an assembly using sequenced reads with 64× coverage (193 Gb, 3 flowcell sequencing) resulted in 3,725 contigs with N50s of 16.7 Mb and a total genome length of 2.8 Gb. It was comparable to a KOREF assembly constructed using PacBio at 62× coverage (188 Gb, 2,695 contigs, and N50s of 17.9 Mb). When we applied Hi-C-derived long-range mapping data, an even higher quality assembly for the 64× coverage was achieved, resulting in 3,179 scaffolds with an N50 of 56.4 Mb. CONCLUSION:The pore-based PromethION approach provided a high-quality chromosome-scale human genome assembly at a low cost with long maximum contig and scaffold lengths and was more cost-effective than PacBio at comparable quality measurements

Depression and suicide risk prediction models using blood-derived multi-omics data

More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 92.6% in distinguishing SAs from MDD patients, 87.3% in distinguishing MDD patients from controls, and 86.7% in distinguishing SAs from controls. We also developed regression models for predicting psychiatric scales with R2 values of 0.961 and 0.943 for Hamilton Rating Scale for Depression???17 and Scale for Suicide Ideation, respectively. Multi-omics data were used to construct psychiatric status prediction models for improved mental health treatment

Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates.

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing

Decoding a highly mixed Kazakh genome.

We provide a Kazakh whole genome sequence (MJS) and analyses with the largest comparative Kazakh genomic data available to date. We found 102,240 novel SNVs and a high level of heterozygosity. ADMIXTURE analysis confirmed a significant proportion of variations in this individual coming from all continents except Africa and Oceania. A principal component analysis showed neighboring Kalmyk, Uzbek, and Kyrgyz populations to have the strongest resemblance to the MJS genome which reflects fairly recent Kazakh history. MJS's mitochondrial haplogroup, J1c2, probably represents an early European and Near Eastern influence to Central Asia. This was also supported by the heterozygous SNPs associated with European phenotypic features and strikingly similar Kazakh ancestral composition inferred by ADMIXTURE. Admixture (f3) analysis showed that MJS's genomic signature is best described as a cross between the Neolithic East Asian (Devil's Gate1) and the Bronze Age European (Halberstadt_LBA1) components rather than a contemporary admixture

The origin and composition of Korean ethnicity analyzed by ancient and present-day genome sequences

Koreans are thought to be an ethnic group of admixed northern and southern subgroups. However, the exact genetic origins of these two remain unclear. In addition, the past admixture is presumed to have taken place on the Korean peninsula, but there is no genomic scale analysis exploring the origin, composition, admixture, or the past migration of Koreans. Here, 88 Korean genomes compared with 91 other present-day populations showed two major genetic components of East Siberia and Southeast Asia. Additional paleogenomic analysis with 115 ancient genomes from Pleistocene hunter-gatherers to Iron Age farmers showed a gradual admixture of Tianyuan (40 ka) and Devil's gate (8 ka) ancestries throughout East Asia and East Siberia up until the Neolithic era. Afterward, the current genetic foundation of Koreans may have been established through a rapid admixture with ancient Southern Chinese populations associated with Iron Age Cambodians. We speculate that this admixing trend initially occurred mostly outside the Korean peninsula followed by continuous spread and localization in Korea, corresponding to the general admixture trend of East Asia. Over 70% of extant Korean genetic diversity is explained to be derived from such a recent population expansion and admixture from the South

Comparative analysis of 7 short-read sequencing platforms using the Korean Reference Genome: MGI and Illumina sequencing benchmark for whole-genome sequencing

Background: DNBSEQ-T7 is a new whole-genome sequencer developed by Complete Genomics and MGI using DNA nanoball and combinatorial probe anchor synthesis technologies to generate short reads at a very large scale-up to 60 human genomes per day. However, it has not been objectively and systematically compared against Illumina short-read sequencers. Findings: By using the same KOREF sample, the Korean Reference Genome, we have compared 7 sequencing platforms including BGISEQ-500, DNBSEQ-T7, HiSeq2000, HiSeq2500, HiSeq4000, HiSeqX10, and NovaSeq6000. We measured sequencing quality by comparing sequencing statistics (base quality, duplication rate, and random error rate), mapping statistics (mapping rate, depth distribution, and percent GC coverage), and variant statistics (transition/transversion ratio, dbSNP annotation rate, and concordance rate with single-nucleotide polymorphism [SNP] genotyping chip) across the 7 sequencing platforms. We found that MGI platforms showed a higher concordance rate for SNP genotyping than HiSeq2000 and HiSeq4000. The similarity matrix of variant calls confirmed that the 2 MGI platforms have the most similar characteristics to the HiSeq2500 platform. Conclusions: Overall, MGI and Illumina sequencing platforms showed comparable levels of sequencing quality, uniformity of coverage, percent GC coverage, and variant accuracy; thus we conclude that the MGI platforms can be used for a wide range of genomics research fields at a lower cost than the Illumina platforms

Welfare Genome Project: A Participatory Korean Personal Genome Project With Free Health Check-Up and Genetic Report Followed by Counseling.

The Welfare Genome Project (WGP) provided 1,000 healthy Korean volunteers with detailed genetic and health reports to test the social perception of integrating personal genetic and healthcare data at a large-scale. WGP was launched in 2016 in the Ulsan Metropolitan City as the first large-scale genome project with public participation in Korea. The project produced a set of genetic materials, genotype information, clinical data, and lifestyle survey answers from participants aged 20-96. As compensation, the participants received a free general health check-up on 110 clinical traits, accompanied by a genetic report of their genotypes followed by genetic counseling. In a follow-up survey, 91.0% of the participants indicated that their genetic reports motivated them to improve their health. Overall, WGP expanded not only the general awareness of genomics, DNA sequencing technologies, bioinformatics, and bioethics regulations among all the parties involved, but also the general public's understanding of how genome projects can indirectly benefit their health and lifestyle management. WGP established a data construction framework for not only scientific research but also the welfare of participants. In the future, the WGP framework can help lay the groundwork for a new personalized healthcare system that is seamlessly integrated with existing public medical infrastructure

The Draft Genome of an Octocoral, Dendronephthya gigantea

Coral reefs composed of stony corals are threatened by global marine environmental changes. However, soft coral communities of octocorallian species, appear more resilient. The genomes of several cnidarians species have been published, including from stony corals, sea anemones, and hydra. To fill the phylogenetic gap for octocoral species of cnidarians, we sequenced the octocoral, Dendronephthya gigantea, a nonsymbiotic soft coral, commonly known as the carnation coral. The D. gigantea genome size is similar to 276 Mb. A high-quality genome assembly was constructed from PacBio long reads (29.85 Gb with 108x coverage) and Illumina short paired-end reads (35.54 Gb with 128x coverage) resulting in the highest N50 value (1.4 Mb) reported thus far among cnidarian genomes. About 12% of the genome is repetitive elements and contained 28,879 predicted protein-coding genes. This gene set is composed of 94% complete BUSCO ortholog benchmark genes, which is the second highest value among the cnidarians, indicating high quality. Based on molecular phylogenetic analysis, octocoral and hexacoral divergence times were estimated at 544 MYA. There is a clear difference in Hox gene composition between these species: unlike hexacorals, the Antp superclass Evx gene was absent in D. gigantea. Here, we present the first genome assembly of a nonsymbiotic octocoral, D. gigantea to aid in the comparative genomic analysis of cnidarians, including stony and soft corals, both symbiotic and nonsymbiotic. The D. gigantea genome may also provide clues to mechanisms of differential coping between the soft and stony corals in response to scenarios of global warming

Polygenic risk score validation using Korean genomes of 265 early-onset acute myocardial infarction patients and 636 healthy controls

Background The polygenic risk score (PRS) developed for coronary artery disease (CAD) is known to be effective for classifying patients with CAD and predicting subsequent events. However, the PRS was developed mainly based on the analysis of Caucasian genomes and has not been validated for East Asians. We aimed to evaluate the PRS in the genomes of Korean early-onset AMI patients (n = 265, age <= 50 years) following PCI and controls (n = 636) to examine whether the PRS improves risk prediction beyond conventional risk factors. Results The odds ratio of the PRS was 1.83 (95% confidence interval [CI]: 1.69-1.99) for early-onset AMI patients compared with the controls. For the classification of patients, the area under the curve (AUC) for the combined model with the six conventional risk factors (diabetes mellitus, family history of CAD, hypertension, body mass index, hypercholesterolemia, and current smoking) and PRS was 0.92 (95% CI: 0.90-0.94) while that for the six conventional risk factors was 0.91 (95% CI: 0.85-0.93). Although the AUC for PRS alone was 0.65 (95% CI: 0.61-0.69), adding the PRS to the six conventional risk factors significantly improved the accuracy of the prediction model (P = 0.015). Patients with the upper 50% of PRS showed a higher frequency of repeat revascularization (hazard ratio = 2.19, 95% CI: 1.47-3.26) than the others. Conclusions The PRS using 265 early-onset AMI genomes showed improvement in the identification of patients in the Korean population and showed potential for genomic screening in early life to complement conventional risk prediction