The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alteration...The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.展开更多
Domesticated sheep have been exposed to artificial selection for the production of fiber, meat, and milk as well as to natural selection. Such selections are likely to have imposed distinctive selection signatures on ...Domesticated sheep have been exposed to artificial selection for the production of fiber, meat, and milk as well as to natural selection. Such selections are likely to have imposed distinctive selection signatures on the sheep genome. Therefore, detecting selection signatures across the genome may help elucidate mechanisms of selection and pinpoint candidate genes of interest for further investigation. Here, detection of selection signatures was conducted in three sheep breeds, Sunite （n=66）, German Mutton （n=159）, and Dorper （n=93）, using the Illumina OvineSNP50 Genotyping BeadChip array. Each animal provided genotype information for 43 273 autosomal single nucleotide polymorphisms （SNPs）. We adopted two complementary haplotype-based statistics of relative extended haplotype homozygosity （REHH） and the cross-popu- lation extended haplotype homozygosity （XP-EHH） tests. In total, 707,755, and 438 genomic regions subjected to positive selection were identified in Sunite, German Mutton, and Dorper sheep, respectively, and 42 of these regions were detected using both REHH and XP-EHH analyses. These genomic regions harbored many important genes, which were enriched in gene ontology terms involved in muscle development, growth, and fat metabolism. Fourteen of these genomic regions overlapped with those identified in our previous genome-wide association studies, further indicating that these genes under positive selection may underlie growth developmental traits. These findings contribute to the identification of candidate genes of interest and aid in understanding the evolutionary and biological mechanisms for controlling complex traits in Chinese and western sheep.展开更多
For structural comparisons of paired prokaryotic genomes,an important topic in synthetic and evolutionary biology,the locations of shared orthologous genes(henceforth orthologs)are observed as binned data.This and oth...For structural comparisons of paired prokaryotic genomes,an important topic in synthetic and evolutionary biology,the locations of shared orthologous genes(henceforth orthologs)are observed as binned data.This and other data,e.g.,wind directions recorded at monitoring sites and intensive care unit arrival times on the 24-hour clock,are counted in binned circular arcs,thus modeling them by discrete circular distributions(DCDs)is required.We propose a novel method to construct a DCD from a base continuous circular distribution(CCD).The probability mass function is defined to take the normalized values of the probability density function at some pre-fixed equidistant points on the circle.Five families of constructed DCDs which have normalizing constants in closed form are presented.Simulation studies show that DCDs outperform the corresponding CCDs in modeling grouped(discrete)circular data,and minimum chi-square estimation outperforms maximum likelihood estimation for parameters.We apply the constructed DCDs,invariant wrapped Poisson and wrapped discrete skew Laplace to compare the structures of paired bacterial genomes.Specifically,discrete four-parameter wrapped Cauchy(nonnegative trigonometric sums)distribution models multi-modal shared orthologs in Clostridium(Sulfolobus)better than the others considered,in terms of AIC and Freedman’s goodness-of-fit test.The result that different DCDs fit the shared orthologs is consistent with the fact they belong to two kingdoms.Nevertheless,these prokaryotes have a common favored site around 70°on the unit circle;this finding is important for building synthetic prokaryotic genomes in synthetic biology.These DCDs can also be applied to other binned circular data.展开更多
Current study adopted gene flow theory and selection index method to compare the breeding efficiency of three breeding plans in the Chinese Holstein cattle using ZPLAN software. Simulated conventional progeny-testing ...Current study adopted gene flow theory and selection index method to compare the breeding efficiency of three breeding plans in the Chinese Holstein cattle using ZPLAN software. Simulated conventional progeny-testing program （PT） and young sire program （YS） were compared with breeding program using genomic selection （GS） taking parameters derived from Chinese Holstein breeding system. The results showed that, GS shortened generation interval by 1.5-2.2 years, and increased the genetic progress by 30-50%, comparing to PT and YS, respectively. Economic analysis showed that GS could obtain a higher breeding efficiency, being 119 and 97% higher than that of PT and YS, respectively; and GS was also powerful in improving functional traits with a low heritability. Main factors affecting breeding efficiency in GS were further discussed, including selection intensity, accuracy and the cost of SNP genotyping. Our finding provided references for future designing and implementing GS in Chinese dairy population.展开更多
Pancreatic ductal adenocarcinoma is speculated to become the second leading cause of cancer-related mortality by 2030,a high mortality rate considering the number of cases.Surgery and chemotherapy are the main treatme...Pancreatic ductal adenocarcinoma is speculated to become the second leading cause of cancer-related mortality by 2030,a high mortality rate considering the number of cases.Surgery and chemotherapy are the main treatment options,but they are burdensome for patients.A clear histological diagnosis is needed to determine a treatment plan,and endoscopic ultrasound(EUS)-guided tissue acquisition(TA)is a suitable technique that does not worsen the cancer-specific prognosis even for lesions at risk of needle tract seeding.With the development of personalized medicine and precision treatment,there has been an increasing demand to increase cell counts and collect specimens while preserving tissue structure,leading to the development of the fine-needle biopsy(FNB)needle.EUS-FNB is rapidly replacing EUS-guided fine-needle aspiration(FNA)as the procedure of choice for EUS-TA of pancreatic cancer.However,EUS-FNA is sometimes necessary where the FNB needle cannot penetrate small hard lesions,so it is important clinicians are familiar with both.Given these recent developments,we present an up-to-date review of the role of EUS-TA in pancreatic cancer.Particularly,technical aspects,such as needle caliber,negative pressure,and puncture methods,for obtaining an adequate specimen in EUS-TA are discussed.展开更多
There is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amoun...There is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amount, origin, as well as some factors affecting the success rate of its amplification, together to provide researchers with a more comprehensive perspective on embryonic cfDNA. The origin of cfDNA in SCM is complicated and poses challenges to the interpretation of genetic test results. Advanced molecular techniques should distinguish between embryonic and contaminated DNA to maximize the success rate of amplification and analysis. Recent data showed that the type of culture medium, assisted hatching or not, the type of amplification kit, and fresh or thawed embryos were not related to the success rate of amplification, but the length of culture time might affect the success rate. The longer culture time, the more cfDNA is available in the SCM. Then we focused on the concordance between trophectoderm (TE), inner cell mass, whole embryo, and embryonic cfDNA. Despite successful amplification, the concordance between TE and embryonic cfDNA was low. In summary, non-invasive genetic testing using SCM could represent a major advance in future single embryo selection, however, contamination and timing for media collection are key factors affecting the results, and current non-invasive cfDNA testing should not be directly applied to clinical practice. Further research is needed to improve the methods used for testing techniques and genetic analysis to achieve greater accuracy and trace its origins before it can be used in the clinics.展开更多
文摘The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.
基金supported by the National Natural Science Foundation of China (31200927)the National Modern Agricultural Industry Technology Fund for Scientists in the Sheep Industry System of China (CARS-39-04B)the Agricultural Science and Technology Innovation Program, China (ASTIP-IAS-TS-6)
文摘Domesticated sheep have been exposed to artificial selection for the production of fiber, meat, and milk as well as to natural selection. Such selections are likely to have imposed distinctive selection signatures on the sheep genome. Therefore, detecting selection signatures across the genome may help elucidate mechanisms of selection and pinpoint candidate genes of interest for further investigation. Here, detection of selection signatures was conducted in three sheep breeds, Sunite （n=66）, German Mutton （n=159）, and Dorper （n=93）, using the Illumina OvineSNP50 Genotyping BeadChip array. Each animal provided genotype information for 43 273 autosomal single nucleotide polymorphisms （SNPs）. We adopted two complementary haplotype-based statistics of relative extended haplotype homozygosity （REHH） and the cross-popu- lation extended haplotype homozygosity （XP-EHH） tests. In total, 707,755, and 438 genomic regions subjected to positive selection were identified in Sunite, German Mutton, and Dorper sheep, respectively, and 42 of these regions were detected using both REHH and XP-EHH analyses. These genomic regions harbored many important genes, which were enriched in gene ontology terms involved in muscle development, growth, and fat metabolism. Fourteen of these genomic regions overlapped with those identified in our previous genome-wide association studies, further indicating that these genes under positive selection may underlie growth developmental traits. These findings contribute to the identification of candidate genes of interest and aid in understanding the evolutionary and biological mechanisms for controlling complex traits in Chinese and western sheep.
基金supported by JSPS KAKENHI Grant Number 18K13459 and Grace S.Shieh was supported in part by MOST 106-2118-M-001-017 and MOST 107-2118-M-001-009-MY2.
文摘For structural comparisons of paired prokaryotic genomes,an important topic in synthetic and evolutionary biology,the locations of shared orthologous genes(henceforth orthologs)are observed as binned data.This and other data,e.g.,wind directions recorded at monitoring sites and intensive care unit arrival times on the 24-hour clock,are counted in binned circular arcs,thus modeling them by discrete circular distributions(DCDs)is required.We propose a novel method to construct a DCD from a base continuous circular distribution(CCD).The probability mass function is defined to take the normalized values of the probability density function at some pre-fixed equidistant points on the circle.Five families of constructed DCDs which have normalizing constants in closed form are presented.Simulation studies show that DCDs outperform the corresponding CCDs in modeling grouped(discrete)circular data,and minimum chi-square estimation outperforms maximum likelihood estimation for parameters.We apply the constructed DCDs,invariant wrapped Poisson and wrapped discrete skew Laplace to compare the structures of paired bacterial genomes.Specifically,discrete four-parameter wrapped Cauchy(nonnegative trigonometric sums)distribution models multi-modal shared orthologs in Clostridium(Sulfolobus)better than the others considered,in terms of AIC and Freedman’s goodness-of-fit test.The result that different DCDs fit the shared orthologs is consistent with the fact they belong to two kingdoms.Nevertheless,these prokaryotes have a common favored site around 70°on the unit circle;this finding is important for building synthetic prokaryotic genomes in synthetic biology.These DCDs can also be applied to other binned circular data.
基金supported by the International S&T Cooperation Program (2008DFA31120)the National Importation of Agriculture Advanced Technology 948 Project of China (2010-C14)+2 种基金the Special Fund for Agro-Scientific Research in the Public Interest,China (nyhyzx07-36)the National Key Technologies R&D Program of China (2006BAD04A01)the Ear-marked Fund for Modern Agro-Industry Technology Research System,China (CARS-37)
文摘Current study adopted gene flow theory and selection index method to compare the breeding efficiency of three breeding plans in the Chinese Holstein cattle using ZPLAN software. Simulated conventional progeny-testing program （PT） and young sire program （YS） were compared with breeding program using genomic selection （GS） taking parameters derived from Chinese Holstein breeding system. The results showed that, GS shortened generation interval by 1.5-2.2 years, and increased the genetic progress by 30-50%, comparing to PT and YS, respectively. Economic analysis showed that GS could obtain a higher breeding efficiency, being 119 and 97% higher than that of PT and YS, respectively; and GS was also powerful in improving functional traits with a low heritability. Main factors affecting breeding efficiency in GS were further discussed, including selection intensity, accuracy and the cost of SNP genotyping. Our finding provided references for future designing and implementing GS in Chinese dairy population.
文摘Pancreatic ductal adenocarcinoma is speculated to become the second leading cause of cancer-related mortality by 2030,a high mortality rate considering the number of cases.Surgery and chemotherapy are the main treatment options,but they are burdensome for patients.A clear histological diagnosis is needed to determine a treatment plan,and endoscopic ultrasound(EUS)-guided tissue acquisition(TA)is a suitable technique that does not worsen the cancer-specific prognosis even for lesions at risk of needle tract seeding.With the development of personalized medicine and precision treatment,there has been an increasing demand to increase cell counts and collect specimens while preserving tissue structure,leading to the development of the fine-needle biopsy(FNB)needle.EUS-FNB is rapidly replacing EUS-guided fine-needle aspiration(FNA)as the procedure of choice for EUS-TA of pancreatic cancer.However,EUS-FNA is sometimes necessary where the FNB needle cannot penetrate small hard lesions,so it is important clinicians are familiar with both.Given these recent developments,we present an up-to-date review of the role of EUS-TA in pancreatic cancer.Particularly,technical aspects,such as needle caliber,negative pressure,and puncture methods,for obtaining an adequate specimen in EUS-TA are discussed.
基金This review was supported by Shanghai Shen Kang Hospital Development Center Municipal Hospital New Frontier Technology Joint Project(SHDC12017105).
文摘There is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amount, origin, as well as some factors affecting the success rate of its amplification, together to provide researchers with a more comprehensive perspective on embryonic cfDNA. The origin of cfDNA in SCM is complicated and poses challenges to the interpretation of genetic test results. Advanced molecular techniques should distinguish between embryonic and contaminated DNA to maximize the success rate of amplification and analysis. Recent data showed that the type of culture medium, assisted hatching or not, the type of amplification kit, and fresh or thawed embryos were not related to the success rate of amplification, but the length of culture time might affect the success rate. The longer culture time, the more cfDNA is available in the SCM. Then we focused on the concordance between trophectoderm (TE), inner cell mass, whole embryo, and embryonic cfDNA. Despite successful amplification, the concordance between TE and embryonic cfDNA was low. In summary, non-invasive genetic testing using SCM could represent a major advance in future single embryo selection, however, contamination and timing for media collection are key factors affecting the results, and current non-invasive cfDNA testing should not be directly applied to clinical practice. Further research is needed to improve the methods used for testing techniques and genetic analysis to achieve greater accuracy and trace its origins before it can be used in the clinics.
