The development of computational biology in South Africa: successes achieved and lessons learnt

Bioinformatics is now a critical skill in many research and commercial environments as biological data are increasing in both size and complexity. South African researchers recognized this need in the mid-1990s and responded by working with the government as well as international bodies to develop initiatives to build bioinformatics capacity in the country. Significant injections of support from these bodies provided a springboard for the establishment of computational biology units at multiple universities throughout the country, which took on teaching, basic research and support roles. Several challenges were encountered, for example with unreliability of funding, lack of skills, and lack of infrastructure. However, the bioinformatics community worked together to overcome these, and South Africa is now arguably the leading country in bioinformatics on the African continent. Here we discuss how the discipline developed in the country, highlighting the challenges, successes, and lessons learnt

p16 Mutation Spectrum in the Premalignant Condition Barrett's Esophagus

Background: Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings: We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions: The results of this study suggest the environment of the esophagus in BE patients can both generate an

First Description of Natural and Experimental Conjugation between Mycobacteria Mediated by a Linear Plasmid

Background: in a previous study, we detected the presence of a Mycobacterium avium species-specific insertion sequence, IS1245, in Mycobacterium kansasii. Both species were isolated from a mixed M. avium-M. kansasii bone marrow culture from an HIV-positive patient. the transfer mechanism of this insertion sequence to M. kansasii was investigated here.Methodology/Principal Findings: A linear plasmid (pMA100) was identified in all colonies isolated from the M. avium-M. kansasii mixed culture carrying the IS1245 element. the linearity of pMA100 was confirmed. Other analyses suggested that pMA100 contained a covalently bound protein in the terminal regions, a characteristic of invertron linear replicons. Partial sequencing of pMA100 showed that it bears one intact copy of IS1245 inserted in a region rich in transposase-related sequences. These types of sequences have been described in other linear mycobacterial plasmids. Mating experiments were performed to confirm that pMA100 could be transferred in vitro from M. avium to M. kansasii. pMA100 was transferred by in vitro conjugation not only to the M. kansasii strain from the mixed culture, but also to two other unrelated M. kansasii clinical isolates, as well as to Mycobacterium bovis BCG Moreau.Conclusions/Significance: Horizontal gene transfer (HGT) is one of most important mechanisms leading to the evolution and diversity of bacteria. This work provides evidence for the first time on the natural occurrence of HGT between different species of mycobacteria. Gene transfer, mediated by a novel conjugative plasmid, was detected and experimentally reproduced.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cooperacion Interuniversitaria UAM-Banco Santander con America Latina (CEAL), UAM, SpainConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilLab Nacl Comp Cient, Petropolis, BrazilUniv Autonoma Madrid, Fac Med, Dept Prevent Med, Madrid, SpainInst Adolfo Lutz Registro, Nucleo TB & Micobacterioses, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilFAPESP: FAPESP - 06/01533-9Web of Scienc

Analysis of the African coelacanth genome sheds light on tetrapod evolution

It was a zoological sensation when a living specimen of the coelacanth was first discovered in 1938, as this lineage of lobe-finned fish was thought to have gone extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features . Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain, and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues demonstrate the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution

p53 and p16/CDKN2 gene mutations in esophageal tumors from a high- incidence area in South Africa

Squamous cell carcinoma of the esophagus has an uneven geographic distribution, with a high incidence in the Transkei region of Eastern Cape Province, South Africa. The precise molecular events associated with tumorigenesis of esophageal cancer in this region have not been characterized. DNA from human esophageal squamous cell carcinomas (n = 76), as well as adjacent tissue samples (n = 9) and blood (n = 50) from the same patients from the Transkei region were screened for somatic mutations. Exons 5-8 of the p53 gene and exons 1-2 of the p16/CDKN2 gene were examined for mutations using PCR-SSCP procedures and DNA sequence analysis. Results show that 17% of the tumors contained small deletions, insertions and point mutations, resulting in frame-shifts or amino acid changes in the p53 gene. Among the mutations in the structural p16/CDKN2 gene, 9 were point mutations, 4 were deletions and 3 were insertions. A novel C to T mutation, 25 bp upstream from the ATG start site of p16/CDKN2, which sometimes occurs together with other structural gene variations, was found. The mutations described here are somatic in origin since none of the DNA samples from the adjacent control tissues or blood samples from the same patients had them.Articl

<it>TP53 </it>mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya

<p>Abstract</p> <p>Background</p> <p>Squamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC) in this area.</p> <p>Results</p> <p>We have analyzed <it>TP53 </it>mutations, the presence of human papilloma virus (HPV) DNA and expression of inflammation markers Cyclooxygenase 2 (Cox-2) and Nitrotyrosine (NTyR) in 28 cases (13 males and 15 females) of archived ESCC tissues collected at the Moi Teaching and Referral Hospital in Eldoret, Kenya. Eleven mutations were detected in <it>TP53 </it>exons 5 to 8 (39%). All ESCC samples were negative for HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82. Immunohistochemical analysis of Cox-2 and NTyR showed a low proportion of positive cases (17.4% and 39.1%, respectively). No association between the above markers and suspected risk factors (alcohol or tobacco use, hot tea drinking, use of charcoal for cooking) was found.</p> <p>Conclusion</p> <p>Our findings suggest that mechanisms of esophageal carcinogenesis in eastern Africa might be different from other parts of the world. Low prevalence of <it>TP53 </it>mutation compared with other intermediate or high incidence areas of the world highlights this hypothesis. Our data did not support a possible ole of HPV in this series of cases. Further studies are needed to assess and compare the molecular patterns of ESCC from Kenya with those of high-incidence areas such as China or Central Asia.</p

Biological Psychiatry Congress 2015

List of Abstract Titles and authors: 1. Psychosis: A matter of mental effort? M Borg, Y Y van der Zee, J H Hsieh, H Temmingh, D J Stein, F M Howells 2.In search of an affordable, effective post-discharge intervention: A randomised control trial assessing the influence of a telephone-based intervention on readmissions for patients with severe mental illness in a developing country U A Botha, L Koen, M Mazinu, E Jordaan, D J H Niehaus 3. The effect of early abstinence from long-term methamphetamine use on brain metabolism using 1H-magnetic resonance spectro-scopy (1H-MRS) A Burger, S Brooks, D J Stein, F M Howells 4. The effect of in utero exposure to methamphetamine on brain metabolism in childhood using 1H-magnetic resonance spectroscopy (1H-MRS) A Burger, A Roos, M Kwiatkowski, D J Stein, K A Donald, F M Howells 5. A prospective study of clinical, biological and functional aspects of outcome in first-episode psychosis: The EONKCS Study B Chiliza, L Asmal, R Emsley 6. Stimulants as cognitive enhancers - perceptions v. evidence in a very real world H M Clark 7. Pharmacogenomics in antipsychotic drugs Ilse du Plessis 8. Serotonin in anxiety disorders and beyond Ilse du Plessis 9. HIV infection results in ventral-striatal reward system hypo-activation during cue processing S du Plessis, M Vink, J A Joska, E Koutsilieri, A Bagadia, D J Stein, R Emsley 10. Disease progression in schizophrenia: Is the illness or the treatment to blame? R Emsley, M J Sian 11. Serotonin transporter variants play a role in anxiety sensitivity in South African adolescents  S M J Hemmings, L I Martin, L van der Merwe, R Benecke, K Domschke, S Seedat 12. Iron deficiency in two children diagnosed with multiple sclerosis: Report on whole exom sequencing S Janse van Rensburg, R van Toorn, J F Schoeman, A Peeters, L R Fisher, K Moremi, M J Kotze 13. Benzodiazepines: Practical pharmacokinetics P Joubert 14. What to consider when prescribing psychotropic medications G Lippi 15. Current prescribing practices for obsessive-compulsive disorder in South Africa: Controversies and consensus C Lochner, L Taljaard, D J Stein 16. Correlates of emotional and behavioural problems in children with preinatally acquired HIV in Cape Town, South Africa K-A Louw, N Phillips, JIpser, J Hoare 17. The role of non-coding RNAs in fear extinction S Malan-Muller, L Fairbairn, W M U Daniels, M J S Dashti, E J Oakleley, M Altorfer, J Harvey, S Seedat, J Gamieldien, S M J Hemmings 18. An analysis of the management og HIV-mental illness comorbidity at the psychiatric unit of the Dr George Mukhari Academic Hospital M L Maodi, S T Rataemane, T Kyaw 19. The identification of novel genes in anxiety disorders: A gene X environment correlation and interaction study N W McGregor, J Dimatelis, S M J Hemmings, C J Kinnear, D J Stein, V Russel, C Lochner 20. Collaborations between conventional medicine and traditional healers: Obstacles and possibilities G Nortje, S Seedat, O Gureje 21. Thought disorder and form perception: Relationships with symptoms and cognitive function in first-episode schizophrenia M R Olivier, R Emsley 22. Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response E Ovenden, B Drogemoller, L van der Merwe, R Emsley, L Warnich 23. The moral and bioethical determinants of "futility" in psychiatry W P Pienaar 24. Single voxel proton magnetic resonance spectroscopy (1H-MRS) and volumetry of the amylgdala in social anxiety disorder in the context of early developmental trauma D Rosenstein, A T Hess, J Zwart, F Ahmed-Leitao, E Meintjies, S Seedat 25. Schizoaffective disorder in an acute psychiatric unit: Profile of users and agreement with Operational Criteria (OPCRIT) R R Singh, U Subramaney 26. The right to privacy and confidentiality: The ethics of expert diagnosis in the public media and the Oscar Pistorius trial C Smith 27. A birth cohort study in South Africa: A psychiatric perspective D J Stein 28. 'Womb Raiders': Women referred for observation in terms of the Criminal Procedures Act (CPA) charged with fetal abduction and murder U Subramaney 29. Psycho-pharmacology of sleep wake disorders: An update R Sykes 30. Refugee post-settlement in South Africa: Role of adjustment challenges and family in mental health outcomes L Thela, A Tomita, V Maharaj, M Mhlongo, K Jonathan 31. Dstinguishing ADHD symptoms in psychotic disorders: A new insight in the adult ADHD questionnaire Y van der Zee, M Borg, J H Hsieh, H Temmingh, D J Stein, F M Howells 32. Oscar Pistorius ethical dilemmas in a trial by media: Does this include psychiatric evaluation by media? M Vorster 33. Genetic investigation of apetite aggression in South African former young offenders: The involvement of serotonin transporter gene K Xulu, J Somer, M Hinsberger, R Weierstall, T Elbert, S Seedat, S Hemmings 34. Effects of HIV and childhood trauma on brain morphemtry and neurocognitive function G Spies, F Ahmed-Leitao, C Fennema-Notestine, M Cherner, S Seedat 35. Measuring intentional behaviour normative data of a newly developed motor task battery S Bakelaar, J Blampain, S Seedat, J van Hoof, Y Delevoye-Turrel 36. Resilience in social anxiety disorder and post-traumatic stress disorder in the context of childhood trauma M Bship, S Bakelaar, D Rosenstein, S Seedat 37. The ethical dilemma of seclusion practices in psychiatry G Chiba, U Subramaney 38. Physical activity and neurological soft signs in patients with schizophrenia O Esan, C Osunbote, I Oladele, S Fakunle, C Ehindero 39. A retrospective study of completed suicides in the Nelson Mandela Bay Metropolitan Area from 2008 to 2013 - preliminary results C Grobler, J Strumpher, R Jacobs 40. Serotonin transporter variants play a role in anxiety sensitivity in South African adolescents S M J Hemmings, L I Martin, L van der Merwe, R Benecke, K Domschke, S Seedat 41. Investigation of variants within antipsychotic candidate pharmacogenes associated with treatment outcome F Higgins, B Drogmoller, G Wright, L van der Merwe, N McGregor, B Chiliza, L Asmal, L Koen, D Niehaus, R Emsley, L Warnich 42. Effects of diet, smoking and alcohol consumption on disability (EDSS) in people diagnosed with multiple sclerosis S Janse van Rensburg, W Davis, D Geiger, F J Cronje, L Whati, M Kidd, M J Kotze 43. The clinical utility of neuroimaging in an acute adolescnet psychiatric inpatient population Z Khan, A Lachman, J Harvey 44. Relationships between childhood trauma (CT) and premorbid adjustment (PA) in a highly traumatised sample of patients with first-episode schizophrenia (FES) S Kilian, J Burns, S Seedat, L Asmal, B Chiliza, S du Plessis, R Olivier, R Emsley 45. Functional and cognitive outcomes using an mTOR inhibitor in an adolescent with TSC A Lachman, C van der Merwe, P Boyes, P de Vries 46. Perceptions about adolescent body image and eating behaviour K Laxton, A B R Janse van Rensburg 47. Clinical relevance of FTO rs9939609 as a determinant of cardio-metabolic risk in South African patients with major depressive disorder H K Luckhoff, M J Kotze 48. Childhood abuse and neglect as predictors of deficits in verbal auditory memory in non-clinical adolescents with low anxiety proneness L Martin, K Martin, S Seedat 49. The changes of pro-inflammatory cytokines in a prenatally stressed febrile seizure animal model and whether Rhus chirindensis may attenuate these changes A Mohamed, M V Mabandla, L Qulu 50. Influence of TMPRSS6 A736v and HFE C282y on serum iron parameters and age of onset in patients with multiple sclerosis K E Moremi, M J Kotze, H K Luckhoff, L R Fisher, M Kidd, R van Toorn, S Janse van Rensburg 51. Polypharmacy in pregnant women with serious mental illness E Thomas, E du Toit, L Koen, D Niehaus 52. Infant attachment and maternal depression as predictors of neurodevelopmental and behavioural outcomes at follow-up J Nothling, B Laughton, S Seedat 53. Differences in abuse, neglect and exposure to community violence in adolescents with and without PTSD J Nothling, S Suliman, L Martin, C Simmons, S Seedat 54. Assessment of oxidative stress markers in children with autistic spectrum disorders in Lagos, Nigeria Y Oshodi, O Ojewunmi, T A Oshodi, T Ijarogbe, O F Aina, J Okpuzor, O C F E A Lesi 55. Change in diagnosis and management of 'gender identity disorder' in pre-adolescent children S Pickstone-Taylor 56. Brain network connectivity in women exposed to intimate partner violence A Roos, J-P Fouche, B Vythilingum, D J Stein 57. Prolonged exposure treatment for PTSD in a Third-World, task-shifting, community-based environment J Rossouw, E Yadin, I Mbanga, T Jacobs, W Rossouw, D Alexander, S Seedat 58. Contrasting effects of early0life stress on mitochondrial energy-related proteins in striatum and hippocampus of a rat model of attention-deficit/ hyperactivity disorder V Russell, J Dimatelis, J Womersley, T-L Sterley 59. Attention-deficit hyperactivity disorder in adults: A South African perspective R Schoeman, M de Klerk, M Kidd 60. Cognitive function in women with HIV infection and early-life stress G Spies, C Fennema-Notestine, M Cherner, S Seedat 61. Changes in functional connectivity networks in bipolar disorder patients after mindfulness-based cognitic therapy J A Starke, C F Beckmann, N Horn 62. Post-traumatic stress disorder, overweight and obesity: A systematic review and meta-analysis S Suliman, L Anthonissen, J Carr, S du Plessis, R Emsley, S M J Hemmings, C Lochner, N McGregor L van den Heuvel, S Seedat 63. The brain and behaviour in a third-trimester equivalent animal model of fetal alcohol spectrum disorders P C Swart, C B Currin, J J Dimatelis, V A Russell 64. Irritability Assessment Model (IAM) to monitor irritability in child and adolescent psychiatric disorders. D van der Westhuizen 65. Outcome of parent-adolescent training in chilhood victimisation: Adaptive functioning, psychosocial and physiological variables D van der Westhuizen 66. The effect of ketamine in the Wistar-Kyoto and Sprague Dawley rat models of depression P J van Zyl, J J Dimatelis, V A Russell 67. Investigating COMT variants in anxiety sensitivity in South African adolescents L J Zass, L Martin, S Seedat, S M J Hemming