Martin Yuille | The University of Manchester (original) (raw)

Papers by Martin Yuille

Human Molecular Genetics, Sep 1, 1992

Biopreservation and biobanking, 2015

Biopreservation and Biobanking, 2015

This socio-economic study is based on the widely held view that there is an inadequate supply of ... more This socio-economic study is based on the widely held view that there is an inadequate supply of human biological samples that is hampering biomedical research development and innovation (RDI). The potential value of samples and the associated data are thus not being realized. We aimed to examine whether the financing of biobanks contributes to this problem and then to propose a national solution. We combined three methods: a qualitative case study; literature analysis; and informal consultations with experts. The case study enabled an examination of the complex institutional arrangements for biobanks, with a particular focus on cost models. For the purposes of comparison, a typology for biobanks was developed using the three methods. We found that it is not possible to apply a standard cost model across the diversity of biobanks, and there is a deficit in coordination and sustainability and an excess of complexity. We propose that coordination across this diversity requires dedicated resources for a national biobanking distributed research infrastructure. A coordination center would establish and improve standards and support a national portal for access. This should be financed centrally by public funds, possibly supplemented by industrial funding. We propose that: a) sample acquisition continues to be costed into projects and project proposals to ensure biobanking is driven by research needs; b) core biobanking activities and facilities be supported by central public funds distributed directly to host public institutions; and c) marginal costs for access be paid for by the user.

Journal of acquired immune deficiency syndromes

In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane exp... more In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.

This paper has three main propositions. First, the success of translational research requires cha... more This paper has three main propositions. First, the success of translational research requires changes in practice and culture by universities, hospitals and industry. Second, biobanking networks are one of the most effective ways of enabling those changes – if the networks have standards that can reach across universities, hospitals and industry. Third, a network quality management system based on ISO9001 requirements can be an effective tool to drive the changes required for a biobanking network to function. The goal of academic biomedical research has been to serve a scientific good: to understand the human organism in health and disease. The goal of clinical and industrial research has been to serve a public good: to develop and innovate for the alleviation of human disease and ill-health. Today, in the rapidly changing landscape of biomedical research, academic researchers are capable of and are being encouraged by society to address both goals. To address two goals in place of ...

In vivo (Athens, Greece)

To investigate the genetics of chronic lymphocytic leukemia (CLL). In 56 (7%) out of 800 CLL pati... more To investigate the genetics of chronic lymphocytic leukemia (CLL). In 56 (7%) out of 800 CLL patients with concomitant malignant hematological disease, 51 families and 141 cases were ascertained. 106 cases (75%) of CLL, 27 cases (19%) of nonCLL and 8 cases (6%) of myeloproliferative disorders. Paternal disease was transmitted primarily to the youngest sons in the sibship while maternal disease was transmitted equally to all sibs, demonstrated by means of matrix conjugation and confirmed with Cox regression on parity and birth order (maternal-offspring combination: relative risk (RR), 95% confidence interval (CI)=1.47 (0.89 - 2.43), p=0.12, compared with paternal-offspring combination: RR=3.25, 95% CI=(1.57-6.72), p<0.001). The B-cell expression in familial and sporadic CLL was indistinguishable. Parental genomic imprinting is pointed out as one possible mechanism behind this non-Mendelian genomic output.

Leukemia, 1996

Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and ch... more Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and chronic lymphoproliferative disorders. In the former, an 8 kb region within the MLL gene is consistently involved, whereas in the latter breakpoints appear to be heterogeneous. In a B cell acute leukemia cell line with t(14;18)(q32.3;q21.3) we have previously demonstrated a reciprocal translocation between the LAZ3/BCL6 gene at 3q27 and the B cell specific transcriptional coactivator gene BOB-1 at 11q23.1, implicating BOB-1 as a potential proto-oncogene. To confirm the chromosomal localization of BOB-1 we have mapped it by FISH to 11q23.1. It lay immediately telomeric of the ATM gene. We have also investigated the frequency of BOB-1 rearrangements in a panel of 32 cell lines and 71 patient samples. In one case of T cell prolymphocytic leukemia-a disease where 11q23 abnormalities are observed-a chromosomal rearrangement was identified 3.3-0.9 kb centromeric of the 3' end of the gene. Th...

Blood, 2000

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis ... more Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blo...

Science translational medicine, Jan 5, 2014

A calculation grid developed by an international expert group was tested across biobanks in six c... more A calculation grid developed by an international expert group was tested across biobanks in six countries to evaluate costs for collections of various types of biospecimens. The assessment yielded a tool for setting specimen-access prices that were transparently related to biobank costs, and the tool was applied across three models of collaborative partnership.

Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer, 1998

The ataxia telangiectasia (A-T) gene, ATM, predisposes affected homozygotes to a wide range of ma... more The ataxia telangiectasia (A-T) gene, ATM, predisposes affected homozygotes to a wide range of malignancies. It has been suggested that this is a consequence of the genomic instability associated with the syndrome. The elevated risk of malignancy is not, however, observed among A-T heterozygotes (except, apparently, regarding breast cancer). In this report we describe results from the study of the rare sporadic disease, T cell prolymphocytic leukaemia (T-PLL). In all individuals tested, we observed that at least one ATM allele was disrupted by rearrangement, that in many cases both alleles were disrupted and that there were additional mutations, predominantly missense, that clustered toward the 3' end of the gene corresponding to the protein's phosphatidylinositol 3-kinase (PIK)-related domain. We conclude that the ATM gene can act as a tumour suppressor in the development of sporadic T-PLL. Our finding of a surfeit of mutations within ATM may reflect the involvement of the ...

Clinical oncology (Royal College of Radiologists (Great Britain)), 2014

Biopreservation and Biobanking, 2012

In biobank networks, accrual, aggregation, and retrieval of samples and data are impeded if minim... more In biobank networks, accrual, aggregation, and retrieval of samples and data are impeded if minimal standards are not agreed in advance by the network members. The critical requirement is that outputs be standardized between biobanks. To start to address this problem of minimal standards, we undertook a pilot study and now report a follow-up study with 79 centers to identify sources of variability in a common measurement-the estimation of DNA concentration. Our main findings include confirmation of the results of the pilot study on overall variability between centers; fluorescence spectroscopy yields lower estimates of concentration and has less accuracy than absorption spectroscopy; and the 2 technologies differ in their sensitivity to mixing of the samples before measurement. We found that more recent servicing of liquid handling devices contributes to accuracy (at least when deploying absorption spectroscopy). We conclude that, while further study is required, there is a need to promote the development of complete Standard Operating Procedures in academic and commercial laboratories with the implementation of management systems that ensure full adherence to those procedures. There also needs to be a consensus on how much variability in measurements is acceptable for each downstream platform for technologies, including genotyping, sequencing, and epigenetics.

Biopreservation and Biobanking, 2012

The UK DNA Banking Network (UDBN) undertakes biobanking for genetic epidemiology research project... more The UK DNA Banking Network (UDBN) undertakes biobanking for genetic epidemiology research projects. A task assigned to it is the addition of scientific value to the resources under its management. This task is implemented by enabling appropriate access to the resources. We reasoned that access requires not only a fair access policy but also a quality policy implemented via a Quality Management System (QMS). UDBN decided to achieve consistency in sample management by identifying and implementing a suitable QMS with external certification. UDBN selected ISO9001 as a QMS. It was soon recognized that the QMS needed to encompass not only UDBN but also the academic department in which UDBN sits. An external certification body was selected and a post was dedicated to the role of QMS-Management Representative. Specialized software was acquired. A Quality Manual, individual training files and Standard Operating Procedures (SOPs) were prepared. QMS training was provided. These actions led to the approval of the ISO9001:2000 standard. This is the first report of an academic genetic epidemiology research laboratory receiving approval of the ISO9001 standard to validate the consistency of its operations. ISO9001 was selected because of its greater breadth of scope compared with other QMSs. We found that while laboratory protocols are transferable between labs, QMS SOPs are not transferable. This has consequences for efforts to ensure consistency across a biobank network: joint adoption of one multiparty QMS is probably required. We found that it was not possible to implement a QMS for biobanking in isolation: its host university department needed to be included. We have found that ISO9001 helps enable longitudinal accrual of data on the use of biobanking methods. Thus ISO9001 is not only a management tool to improve access to a biobanking research infrastructure but also a research tool for research infrastructure development.

Biopreservation and biobanking, 2010

Cell and tissue banking, 2010

The UK DNA Banking Network (UDBN) is a secondary biobank: it aggregates and manages resources (sa... more The UK DNA Banking Network (UDBN) is a secondary biobank: it aggregates and manages resources (samples and data) originated by others. The network comprises, on the one hand, investigator groups led by clinicians each with a distinct disease specialism and, on the other hand, a research infrastructure to manage samples and data. The infrastructure addresses the problem of providing secure quality-assured accrual, storage, replenishment and distribution capacities for samples and of facilitating access to DNA aliquots and data for new peer-reviewed studies in genetic epidemiology. 'Fair access' principles and practices have been pragmatically developed that, unlike open access policies in this area, are not cumbersome but, rather, are fit for the purpose of expediting new study designs and their implementation. UDBN has so far distributed >60,000 samples for major genotyping studies yielding…

Human Molecular Genetics, Sep 1, 1992

Biopreservation and biobanking, 2015

Biopreservation and Biobanking, 2015

This socio-economic study is based on the widely held view that there is an inadequate supply of ... more This socio-economic study is based on the widely held view that there is an inadequate supply of human biological samples that is hampering biomedical research development and innovation (RDI). The potential value of samples and the associated data are thus not being realized. We aimed to examine whether the financing of biobanks contributes to this problem and then to propose a national solution. We combined three methods: a qualitative case study; literature analysis; and informal consultations with experts. The case study enabled an examination of the complex institutional arrangements for biobanks, with a particular focus on cost models. For the purposes of comparison, a typology for biobanks was developed using the three methods. We found that it is not possible to apply a standard cost model across the diversity of biobanks, and there is a deficit in coordination and sustainability and an excess of complexity. We propose that coordination across this diversity requires dedicated resources for a national biobanking distributed research infrastructure. A coordination center would establish and improve standards and support a national portal for access. This should be financed centrally by public funds, possibly supplemented by industrial funding. We propose that: a) sample acquisition continues to be costed into projects and project proposals to ensure biobanking is driven by research needs; b) core biobanking activities and facilities be supported by central public funds distributed directly to host public institutions; and c) marginal costs for access be paid for by the user.

Journal of acquired immune deficiency syndromes

In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane exp... more In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.

This paper has three main propositions. First, the success of translational research requires cha... more This paper has three main propositions. First, the success of translational research requires changes in practice and culture by universities, hospitals and industry. Second, biobanking networks are one of the most effective ways of enabling those changes – if the networks have standards that can reach across universities, hospitals and industry. Third, a network quality management system based on ISO9001 requirements can be an effective tool to drive the changes required for a biobanking network to function. The goal of academic biomedical research has been to serve a scientific good: to understand the human organism in health and disease. The goal of clinical and industrial research has been to serve a public good: to develop and innovate for the alleviation of human disease and ill-health. Today, in the rapidly changing landscape of biomedical research, academic researchers are capable of and are being encouraged by society to address both goals. To address two goals in place of ...

In vivo (Athens, Greece)

To investigate the genetics of chronic lymphocytic leukemia (CLL). In 56 (7%) out of 800 CLL pati... more To investigate the genetics of chronic lymphocytic leukemia (CLL). In 56 (7%) out of 800 CLL patients with concomitant malignant hematological disease, 51 families and 141 cases were ascertained. 106 cases (75%) of CLL, 27 cases (19%) of nonCLL and 8 cases (6%) of myeloproliferative disorders. Paternal disease was transmitted primarily to the youngest sons in the sibship while maternal disease was transmitted equally to all sibs, demonstrated by means of matrix conjugation and confirmed with Cox regression on parity and birth order (maternal-offspring combination: relative risk (RR), 95% confidence interval (CI)=1.47 (0.89 - 2.43), p=0.12, compared with paternal-offspring combination: RR=3.25, 95% CI=(1.57-6.72), p<0.001). The B-cell expression in familial and sporadic CLL was indistinguishable. Parental genomic imprinting is pointed out as one possible mechanism behind this non-Mendelian genomic output.

Leukemia, 1996

Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and ch... more Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and chronic lymphoproliferative disorders. In the former, an 8 kb region within the MLL gene is consistently involved, whereas in the latter breakpoints appear to be heterogeneous. In a B cell acute leukemia cell line with t(14;18)(q32.3;q21.3) we have previously demonstrated a reciprocal translocation between the LAZ3/BCL6 gene at 3q27 and the B cell specific transcriptional coactivator gene BOB-1 at 11q23.1, implicating BOB-1 as a potential proto-oncogene. To confirm the chromosomal localization of BOB-1 we have mapped it by FISH to 11q23.1. It lay immediately telomeric of the ATM gene. We have also investigated the frequency of BOB-1 rearrangements in a panel of 32 cell lines and 71 patient samples. In one case of T cell prolymphocytic leukemia-a disease where 11q23 abnormalities are observed-a chromosomal rearrangement was identified 3.3-0.9 kb centromeric of the 3' end of the gene. Th...

Blood, 2000

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis ... more Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blo...

Science translational medicine, Jan 5, 2014

A calculation grid developed by an international expert group was tested across biobanks in six c... more A calculation grid developed by an international expert group was tested across biobanks in six countries to evaluate costs for collections of various types of biospecimens. The assessment yielded a tool for setting specimen-access prices that were transparently related to biobank costs, and the tool was applied across three models of collaborative partnership.

Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer, 1998

The ataxia telangiectasia (A-T) gene, ATM, predisposes affected homozygotes to a wide range of ma... more The ataxia telangiectasia (A-T) gene, ATM, predisposes affected homozygotes to a wide range of malignancies. It has been suggested that this is a consequence of the genomic instability associated with the syndrome. The elevated risk of malignancy is not, however, observed among A-T heterozygotes (except, apparently, regarding breast cancer). In this report we describe results from the study of the rare sporadic disease, T cell prolymphocytic leukaemia (T-PLL). In all individuals tested, we observed that at least one ATM allele was disrupted by rearrangement, that in many cases both alleles were disrupted and that there were additional mutations, predominantly missense, that clustered toward the 3' end of the gene corresponding to the protein's phosphatidylinositol 3-kinase (PIK)-related domain. We conclude that the ATM gene can act as a tumour suppressor in the development of sporadic T-PLL. Our finding of a surfeit of mutations within ATM may reflect the involvement of the ...

Clinical oncology (Royal College of Radiologists (Great Britain)), 2014

Biopreservation and Biobanking, 2012

In biobank networks, accrual, aggregation, and retrieval of samples and data are impeded if minim... more In biobank networks, accrual, aggregation, and retrieval of samples and data are impeded if minimal standards are not agreed in advance by the network members. The critical requirement is that outputs be standardized between biobanks. To start to address this problem of minimal standards, we undertook a pilot study and now report a follow-up study with 79 centers to identify sources of variability in a common measurement-the estimation of DNA concentration. Our main findings include confirmation of the results of the pilot study on overall variability between centers; fluorescence spectroscopy yields lower estimates of concentration and has less accuracy than absorption spectroscopy; and the 2 technologies differ in their sensitivity to mixing of the samples before measurement. We found that more recent servicing of liquid handling devices contributes to accuracy (at least when deploying absorption spectroscopy). We conclude that, while further study is required, there is a need to promote the development of complete Standard Operating Procedures in academic and commercial laboratories with the implementation of management systems that ensure full adherence to those procedures. There also needs to be a consensus on how much variability in measurements is acceptable for each downstream platform for technologies, including genotyping, sequencing, and epigenetics.

Biopreservation and Biobanking, 2012

The UK DNA Banking Network (UDBN) undertakes biobanking for genetic epidemiology research project... more The UK DNA Banking Network (UDBN) undertakes biobanking for genetic epidemiology research projects. A task assigned to it is the addition of scientific value to the resources under its management. This task is implemented by enabling appropriate access to the resources. We reasoned that access requires not only a fair access policy but also a quality policy implemented via a Quality Management System (QMS). UDBN decided to achieve consistency in sample management by identifying and implementing a suitable QMS with external certification. UDBN selected ISO9001 as a QMS. It was soon recognized that the QMS needed to encompass not only UDBN but also the academic department in which UDBN sits. An external certification body was selected and a post was dedicated to the role of QMS-Management Representative. Specialized software was acquired. A Quality Manual, individual training files and Standard Operating Procedures (SOPs) were prepared. QMS training was provided. These actions led to the approval of the ISO9001:2000 standard. This is the first report of an academic genetic epidemiology research laboratory receiving approval of the ISO9001 standard to validate the consistency of its operations. ISO9001 was selected because of its greater breadth of scope compared with other QMSs. We found that while laboratory protocols are transferable between labs, QMS SOPs are not transferable. This has consequences for efforts to ensure consistency across a biobank network: joint adoption of one multiparty QMS is probably required. We found that it was not possible to implement a QMS for biobanking in isolation: its host university department needed to be included. We have found that ISO9001 helps enable longitudinal accrual of data on the use of biobanking methods. Thus ISO9001 is not only a management tool to improve access to a biobanking research infrastructure but also a research tool for research infrastructure development.

Biopreservation and biobanking, 2010

Cell and tissue banking, 2010

The UK DNA Banking Network (UDBN) is a secondary biobank: it aggregates and manages resources (sa... more The UK DNA Banking Network (UDBN) is a secondary biobank: it aggregates and manages resources (samples and data) originated by others. The network comprises, on the one hand, investigator groups led by clinicians each with a distinct disease specialism and, on the other hand, a research infrastructure to manage samples and data. The infrastructure addresses the problem of providing secure quality-assured accrual, storage, replenishment and distribution capacities for samples and of facilitating access to DNA aliquots and data for new peer-reviewed studies in genetic epidemiology. 'Fair access' principles and practices have been pragmatically developed that, unlike open access policies in this area, are not cumbersome but, rather, are fit for the purpose of expediting new study designs and their implementation. UDBN has so far distributed >60,000 samples for major genotyping studies yielding…