Category Archives: Genome

A research team led by a University of Massachusetts Amherst scientist has made a significant genetic discovery that sheds light on the use of the drug caspofungin to treat a deadly fungal infection, Aspergillus fumigatus, which kills some 100,000 severely immunocompromised people each year.

Typically, healthy people inhale about 50 to 100 spores of A. fumigatus every day when outdoors. Our body does a great job of identifying them and destroying them, says UMass Amherst associate professor of food science John Gibbons, whose microbial genomics lab studies the fungus.

But in people with compromised immune systems from cancer treatment, organ transplants, HIV, COVID-19 and other conditions, A. fumigatus can cause a really nasty infection, invasive pulmonary aspergillosis, with a 50% mortality rate, Gibbons says. And theres a limited way to treat these infections.

To complicate matters, when given in high concentrations as a treatment for an A. fumigatus infection, the anti-fungal drug sometimes creates a caspofungin paradoxical effect [CPE], which increases the fungal growth rather than eradicating it.

In research published in the journal Microbiology Spectrum, senior author Gibbons, Shu Zhao, a former graduate student in the Gibbons lab, and colleagues describe a first important step in the effort to understand when and why treatment with caspofungin could be more harmful than beneficial. The team, including scientists from Vanderbilt University, the University of Tennessee Science Health Center and the University of So Paolo in Brazil, completed the first genomic and molecular identification of two genes that contribute to the paradoxical effect in A. fumigatus.

This is one of the first studies to apply genome-wide association (GWA) analysis to identify genes involved in an Aspergillus fumigatus phenotype, the paper states.

The team sequenced the genome of 67 clinical samples, about half of which had CPE, spotting genetic differences between the groups and then using GWA, a statistical method, to determine how these genetic variants are associated with growth patterns at high concentrations of caspofungin. We identified a few candidate genes that we thought might contribute to this paradoxical effect, Gibbons says.

The scientists then used the genetic engineering technology, CRISPR, to delete those candidate genes from the genome, creating gene-deletion mutants and enabling the researchers to determine that two of the genes were involved in the paradoxical effect.

It looks like there are many genes and many genetic variants that contribute to this phenotype, Gibbons says. We arent done yet. One idea is that we could potentially generate new drug targets if we find the full collection of genes. We dont understand the mechanisms yet.

Ultimately the team hopes they can use DNA sequencing to understand the genetic basis of different phenotypes in general and to predict for clinical benefits if a patient sample of A. fumigatus has a genotype that is associated with the paradoxical effect.

That would be an important tool that could really improve treatment, Gibbons says.

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Genomic Research Aids in the Effort to Understand How Best to Treat Deadly Infections Caused by a Fungus - UMass News and Media Relations

The department of biotechnology (DBT) on Tuesday issued standard operating procedures (SOPs) for research and development (R&D) on certain types of genome edited plants, which is expected to accelerate crop yields and agricultural productivity.

The environment ministry, in a notification in March 2022, had exempted certain types of genome-edited crops from the stringent biosafety regulations applicable to genetically-modified (GM) crops. The ministry had exempted site directed nuclease (SDN) 1 and 2 genomes from rules 7-11 of the Environment Protection Act, thus avoiding a long process for approval of genetically modified (GM) crops through the Genetic Engineering Appraisal Committee (GEAC). So a large area of research on genome edited crops will now be freed from the stricter regulatory norms meant for GM crops.

The SOPs, issued in line with the notification, provide for a regulatory road map and requirement for R&D to meet the threshold for exemptions of genome edited plants under the SDN1 OR SDN 2 categories.

These SOPs for R&D under contained conditions were prepared by an expert committee set up by the DBT and include protocol to show that the genome edited plants are free from exogenously introduced DNA.

This technology will fast track the development of genome edited crops which would help save natural resources and improve efficiency in use of agro-chemicals, K C Bansal, former director, National Bureau of Plant Genetics Resources, told FE.

Also read: Exporters weigh impact of fresh sanctions on Russia with concern

Bansal who was also part of the expert committee constituted to draft SOPs for genome edited crops said that the conventional breeding technique takes 810 years for development of new agricultural crop varieties, while through genome-editing, the new varieties could be developed in two to three years.

Scientists at the Indian Council for Agricultural Research has said the technology has great promise and emphasis is needed on improving oilseed and pulse crop varieties resistant to diseases, insects or pests, and tolerant to drought, salinity and heat stresses.

Scientists say that genome-edited plants are different from genetically-modified organisms (GMO) technology. Genome editing is a group of technologies that gives scientists the ability to change an organisms DNA.

Recently, on the gene editing technology, Johannes D Rossouw, head, vegetables (research and development), Bayer Crop Science, had told FE, we can get that to a point where seed companies, including us, have the ability to use that in their breeding programmes, to again accelerate the products we develop to improve the profitability for growers.

According to Bhagirath Choudhary, founder and director, South Asia Biotechnology Centre, Jodhpur said having a regulatory system in place after a decade of deliberation on genome edited plants would pave a way for advancement such products relevant for Indias need to cope up with climate vagaries, drought and submergence, disease resistance, quality and biofortification.

Choudhary had stated that the SOP aligns and harmonizes Indias regulatory framework on genome editing with other major food producing countries from Latin America, North America, Africa and Asian countries.

Last year, a group of scientists wrote to the PM, for ease of release of the technology.

In the case of GM technology, applicants have to apply to the GEAC, which follows time-consuming testing methods along with states. Till now, cotton is the only GM crop that has been approved for commercial cultivation in the country.

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New R&D norms to fast-track research on genome-edited crops - The Financial Express

Studying M. tuberculosis latency in humans is harsh due to the difficulty of isolating the dormant bacteria, which is not possible until the active disease. Much has been published regarding latent TB and the percentages of reactivation and disease, but the latency data in patients who have already passed the disease have not been studied. Different approaches were used to mimic this process10,11,12. This work shows, for the first time, results obtained using isolates of patients with recurrent TB. Aragon, a region in the North of Spain, has a low incidence of TB. Thanks to the surveillance protocol carried out in this region since 2004, all M. tuberculosis isolates are genotyped and registered, allowing to trace the clinical TB history of the patients. Around 5% of the TB cases in our population correspond to recurrent TB. Of them, 89.8% were TB cases with isolates showing identical IS6110-RFLP patterns, indicating a potential relapse. Most of them (71%) were later considered as fail of treatment. In contrast, 10.2% of the patients had isolates with different genotypes, considered as reinfections. Among the total of TB cases in our community, reinfection occurs in 0.5% of the TB cases, reflecting that reinfection is uncommon among our population. These data are in agreement with a previous study in Madrid population, which showed an 87.5% of relapses and 12.5% of reinfections among the cases with recurrent TB13. However, in a study in the Canary Islands, the results showed a higher reinfection percentage (44%) versus the 55% of relapses14. A more extreme result was obtained in a study in London, in which 72.6% of the repeated patients were classified as reinfections against a 27.4% of relapses15. The large variation of the results among the different studies suggests that they largely depend on the population sample studied. It would be very interesting to analyse the reinfection cases in each of the studies to understand the reasons for these differences. Regarding endemic TB regions, a higher percentage of recurrent TB was found. Around 9.5% of TB patients had recurrent TB in Malawi (39.6% had relapse and 14.4% reinfection, the rest was undetermined)16 and a study carried out in India demonstrated that the majority of relapses they had were among HIV negative people (95% of TB recurrences) while the majority of reinfections were among HIV positive people (75% of TB recurrences)17.

Regarding the epidemiological and risk factors of the relapsed TB cases studied, we found that relapse was significantly earlier in HIV positive patients (in the first two years since the first episode) when compared to HIV negative patients (p value=0.041), what would be in accordance with a compromised immune system. We also found a trend that males suffered relapse earlier than females, which could be linked to other risk factors such as the use of IV drugs, smoking and the HIV status, which were more frequent in males in our study population. Any risk factor was found as significant for causing an earlier reactivation by Colangeli et al. 12, however they recognized that the clinical cases studied did not have in general any comorbidity.

The number of SNPs between the pairs ranged from 0 to 8. Remarkably, three among the 18 pairs had more than 5 SNPs between the first and the relapsed isolate, interpreted as not recent transmission18, even though the bacteria were isolated from the same patient. This could be related to clinical characteristics of the patients, as immunosuppression, HIV status or the treatment adherence. Surprisingly, several SNPs were found in the first isolates that were absent in the relapsed isolates, as if they had reverted. This phenomenon was extreme in P12, in which six out of the seven SNPs found were absent in the relapsed isolate. The explanation could be the presence of different clones in the patient19,20. In this way, in the different disease episodes a different clone was isolated, resulting from different bottlenecks and selective pressures of the original strain21,22. The reinfection with an identical strain has been described as a limitation of these kind of studies, but in our case, it can be discarded as only one of the pairs belonged to a large endemic cluster (P4, with 0 SNPs). The rest of the pairs were infected with orphan or small-outbreak strains of up to four cases, differently from other studies with large endemic clusters and high TB prevalence22.

Same as Colangeli et at.12, we did not find a significant correlation between the number of SNPs and the time between episodes. However, it is possible that P8 (160months between episodes and 0 SNPs) is altering the trend of SNP accumulation when the time between episodes increases. This is one limitation when working with small sample size, that a single point could have a great impact in the results. None of the SNPs found seemed related with recurrence as all were unique and therefore not common to more than one pair of isolates. It has been described that 0.5 SNPs per genome, per year is the standard mutation rate for M. tuberculosis10. Some studies, where multiple MDR/XDR isolates coming from the same patients were sequenced, have reported that selective pressure and antibiotic resistance can increase this mutation rate as high as more than 3 SNPs17,21. Despite all strains had been under the selective pressure of treatment, they did not achieve such a higher rate, maybe because they were drug susceptible. The mean mutation rate found in our study was 0.64 SNPs, slightly above the standard, due to the high mutation rate found in L4.1, almost double than the standard.

The correlation between the mutation rate and the relapsing period was found just marginally significant (p value=0.0613), differently to Colangeli et al.12, who found it significant. It is important to remark that the approaches were completely different: they used transmission events to mimic the latency period as the time between the diagnosis of the two cases, while we used isolates from the same patient who had a previous TB episode. We eliminated all patients with less than one year between the diagnosis of the episodes, as this was considered as a treatment failure, while Colangeli et al. 2020 had latency periods from one month, which was not possible in our clinical cases as a minimum of 6months of treatment was required. We did not find a significant correlation between the mutation rate along the variable generation times analysed when we split the data into [12years] and (214years), we observed just a small difference. This difference was much smaller than that found by Colangeli et al. 2020 (as high as 81010 for early latency), suggesting that mutation rate was constant during the relapsing period in recurrent TB cases. The mutation rate found in our study, 2.71010, was similar to that found by Ford et al. 2011 (21010)10, therefore both more distant from the one found by Colangeli et al. 2020. The reason why our results are similar to those of Ford et al. 2011 could be due to the similarity of the approaches applied, as they used lesions of the same macaques for studying latency and we used relapsed isolates from the same patients.

The analysis of the IS6110 element showed differences in the number of IS6110 copies in six of the pairs studied, affecting more than one IS copy in several pairs. It has been observed that IS6110 transposed more in great starvation conditions23, which could be similar to the conditions the mycobacteria found in the granuloma4. It was surprising that in four of the pairs studied, the relapsed isolates had lost 1 to 3 copies that were present in the first isolates. Noteworthy, the number of reads obtained in the fastQ files for these copies was considerably lower than for the rest of the IS copies. This suggests that those lost copies were not still fixed in the complete bacteria population, therefore a selection among the different clones present in the same patient had taken place24. It could be that the lost copies in the relapsed isolates had some deleterious effect for the mycobacteria as the relapsed bacteria were the ones without that IS copies. The fact that five out of the six pairs with IS6110 movements had more than 2years of relapsing period supports the idea of IS transposing more during the asymptomatic state of the patient23.

The main limitation to analyse the evolution of the bacteria during the dormancy period is the approach used for resembling this state. There is not a perfect approach, as it is impossible to reproduce what is happening inside the granuloma of a concrete patient, but we think that using isolates of the same patient is the closest way to do it. The difficulty to obtain the complete epidemiological information of the patients is another limitation because it does not allow to determine the accurate development of the diseases episodes. Another limitation is that some of the SNPs could be the result of a sequencing error or due to laboratory management, what would have a huge impact on the mutation rate. In addition, although there were more cases of potential relapses in our records, DNA of the isolates was not available. We decided not to re-cultivate these stored isolates to avoid more manipulation that could introduce errors such as additional SNPs that were not present in the original strains.

As a conclusion, the patients with HIV seemed to suffer reactivation in the first two years after the initial episode of TB more frequently than HIV negative patients. Besides, IS6110 movements occurred more frequently in patients with more than two years between episodes and it seems that different clones of the original strain could be responsible for the first and the following episodes. No correlation was found between the number of SNPs and the time between episodes, neither between the mutation rate and the relapsing period, just a trend of diminishing in longer time periods. Finally, the mutation rate seemed to be constant along all the period between episodes.

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Estimation of the mutation rate of Mycobacterium tuberculosis in cases with recurrent tuberculosis using whole genome sequencing | Scientific Reports...

SAN DIEGO, Oct. 06, 2022 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) today announced its participation at theSpanish Society of Hematology (SEHH) 2022 Conference, with six scientific presentations from independent researchers covering a wide variety of the cancer genomics landscape, highlighting the application of optical genome mapping (OGM) for hematologic malignancies and cancer research.

SEHH 2022 is a three-day conference dedicated to basic, preclinical and translational cancer research. SEHH sessions will take place October 6-8, 2022 in Barcelona, Spain. Six separate scientific presentations delivered by faculty and clinicians from Spanish hematology institutes, cancer centers and hospitals will illustrate the application of Bionanos OGM solutions in blood cancer research areas including leukemias, lymphomas and myelofibrosis.

Scientific presentations on OGM include:

More details on the conference can be found here.

We believe the information covered in these SEHH presentations demonstrates the potential of OGM becoming an essential tool in the arsenal of cancer researchers across Spain, commentedErik Holmlin, president and chief executive officer of Bionano. These presentations point to the continued expansion of OGM into clinical research applications for hematological malignancies and we are excited to see how much more of an impact OGM may make in the future.

About Bionano Genomics

Bionano Genomics is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Companys mission is to transform the way the world sees the genome through OGM solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen d/b/a Bionano Laboratories business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. Through its BioDiscovery business, the Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants and absence of heterozygosity across the genome in one consolidated view. For more information, visit http://www.bionanogenomics.com, http://www.bionanolaboratories.comor http://www.biodiscovery.com.

Forward-Looking Statements of Bionano Genomics

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as believe, potential, may, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the utility of OGM in cancer and hematologic research. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive technologies or improvements to existing technologies; failure of the adoption of OGM as a tool for cancer or hematologic research; future study results contradicting the results reported in the presentations given and posters made available at the SEHH 2022 Conference; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2021 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations:Amy ConradJuniper Point+1 (858) 366-3243amy@juniper-point.com

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Bionano Genomics Announces Six User Presentations of OGM Results in Cancer Genomics Research at the Spanish Society of Hematology (SEHH) 2022 -...

Every modern mammal, from a platypus to a blue whale, is descended from a common ancestor that lived about 180 million years ago. We dont know a great deal about this animal, but the organization of its genome has now been computationally reconstructed by an international team of researchers. The work is published Sept. 30 in Proceedings of the National Academy of Sciences.

Our results have important implications for understanding the evolution of mammals and for conservation efforts, said Harris Lewin, distinguished professor of evolution and ecology at the University of California, Davis, and senior author on the paper.

The researchers drew on high-quality genome sequences from 32 living species representing 23 of the 26 known orders of mammals. They included humans and chimps, wombats and rabbits, manatees, domestic cattle, rhinos, bats and pangolins. The analysis also included the chicken and Chinese alligator genomes as comparison groups. Some of these genomes are being produced as part of the Earth BioGenome Project and other large-scale biodiversity genome sequencing efforts. Lewin chairs the Working Group for the Earth BioGenome Project.

The reconstruction shows that the mammal ancestor had 19 autosomal chromosomes, which control the inheritance of an organisms characteristics outside of those controlled by sex-linked chromosomes, (these are paired in most cells, making 38 in total) plus two sex chromosomes, said Joana Damas, first author on the study and a postdoctoral researcher at the UC Davis Genome Center. The team identified 1,215 blocks of genes that consistently occur on the same chromosome in the same order across all 32 genomes. These building blocks of all mammal genomes contain genes that are critical to developing a normal embryo, Damas said.

The researchers found nine whole chromosomes, or chromosome fragments in the mammal ancestor whose order of genes is the same in modern birds chromosomes.

This remarkable finding shows the evolutionary stability of the order and orientation of genes on chromosomes over an extended evolutionary timeframe of more than 320 million years, Lewin said.

In contrast, regions between these conserved blocks contained more repetitive sequences and were more prone to breakages, rearrangements and sequence duplications, which are major drivers of genome evolution.

Ancestral genome reconstructions are critical to interpreting where and why selective pressures vary across genomes. This study establishes a clear relationship between chromatin architecture, gene regulation and linkage conservation, said Professor William Murphy, Texas A&M University, who was not an author on the paper. This provides the foundation for assessing the role of natural selection in chromosome evolution across the mammalian tree of life.

The researchers were able to follow the ancestral chromosomes forward in time from the common ancestor. They found that the rate of chromosome rearrangement differed between mammal lineages. For example, in the ruminant lineage (leading to modern cattle, sheep and deer) there was an acceleration in rearrangement 66 million years ago, when an asteroid impact killed off the dinosaurs and led to the rise of mammals.

The results will help understanding the genetics behind adaptations that have allowed mammals to flourish on a changing planet over the last 180 million years, the authors said.

Additional co-authors on the paper are: Marco Corbo, UC Davis; Jaebum Kim, Konkuk University, Seoul; Jason Turner-Maier, Bruce Birren, Diane Genereux, Jeremy Johnson, Kerstin Lindblad-Toh and Elinor Karlsson, Broad Institute of MIT and HarvardUniversity; Marta Farr, University of Kent, U.K.; Denis Larkin, University of London, U.K.; Oliver Ryder, Marlys Houck, Shaune Hall, Lily Shiue, Stephen Thomas, Thomas Swale, Mark Daly and Cynthia Steiner, San Diego Zoo Wildlife Alliance; Jonas Korlach, Pacific Biosciences; Marcela Uliano-Silva, Wellcome Trust Sanger Institute, Cambridge, U.K.; Camila J. Mazzoni, Berlin Center for Genomics in Biodiversity Research; Martin T. Nweeia, Harvard University and the Smithsonian Institution; and Rebecca Johnson, Australian Museum and University of Sydney; and members of the Zoonomia Consortium. The work was partly supported by the U.S. Department of Agriculture.

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Revealing the Genome of the Common Ancestor of All Mammals - University of California, Davis

The study also identified a new prostate cancer taxonomy.

Two groundbreaking studies recentlypublished in the journalsNature and Genome Medicine found genetic signatures that explain ethnic disparities in the severity of prostate cancer, notably in Sub-Saharan Africa.

By genetically analyzing prostate cancer tumors from Australian, Brazilian, and South African donors, the team developed a new prostate cancer taxonomy (classification scheme) and cancer drivers that not only distinguish patients based on their genetic ancestry but also predict which cancers are likely to become life-threatening, a task that is currently difficult.

Our understanding of prostate cancer has been severely limited by a research focus on Western populations, said senior author Professor Vanessa Hayes, genomicist and Petre Chair of Prostate Cancer Research at the University of Sydneys Charles Perkins Centre and Faculty of Medicine and Health in Australia. Being of African descent, or from Africa, more than doubles a mans risk for lethal prostate cancer. While genomics holds a critical key to unraveling contributing genetic and non-genetic factors, data for Africa has till now, been lacking.

Professor Vanessa Hayes examining a blood sample from a prostate cancer patient that was used in the study. Credit: Stefanie Zingsheim, University of Sydney

Prostate cancer is the silent killer in our region, said University of Pretorias Professor Riana Bornman, an international expert in mens health and clinical lead for the Southern African Prostate Cancer Study in South Africa. We had to start with a grassroots approach, engaging communities with open discussion, establishing the infrastructure for African inclusion in the genomic revolution, while determining the true extent of prostate disease.

Over two million cancer-specific genomic variants were identified in 183 untreated prostate tumors from males residing throughout the three research zones using advanced whole genome sequencing (a method of mapping the full genetic code of cancer cells).

We found Africans to be impacted by a greater number and spectrum of acquired (including cancer driver) genetic alterations, with significant implications for ancestral consideration when managing and treating prostate cancer, said Professor Hayes.

Using cutting-edge computational data science which allowed for pattern recognition that included all types of cancer variants, we revealed a novel prostate cancer taxonomy which we then linked to different disease outcomes, said Dr. Weerachai Jaratlerdsiri, a computational biologist from the University of Sydney and first author on the Nature paper.

Combining our unique dataset with the largest public data source of European and Chinese cancer genomes allowed us to, for the first time, place the African prostate cancer genomic landscape into a global context.

As part of her Ph.D. at the University of Sydney, Dr. Tingting Gong, the first author of the Genome Medicine paper, painstakingly sifted through the genomic data for large changes in the structure of chromosomes (molecules that hold genetic information). These changes are often overlooked because of the complexity involved in computationally predicting their presence, but are an area of critical importance and contribution to prostate cancer.

We showed significant differences in the acquisition of complex genomic variation in African and European derived tumors, with consequences for disease progression and new opportunities for treatment, said Dr. Gong.

This cancer genome resource is possibly the first and largest to include African data, in the world.

Through African inclusion, we have made the first steps not only towards globalizing precision medicine but ultimately to reducing the impact of prostate cancer mortality across rural Africa, explains Professor Bornman.

A strength of this study was the ability to generate and process all data through a single technical and analytical pipeline, added Professor Hayes.

The research featured in the Nature and Genome Medicine paper is part of the legacy of the late Archbishop Emeritus Desmond Tutu. He was the first African to have his complete genome sequenced, data which would be an integral part of genetic sequencing and prostate cancer research in southern Africa.

The results of the sequencing were published in Nature in 2010.

Diagnosed at age 66 with advanced prostate cancer, to which he succumbed in late December 2021, the Archbishop was an advocate not only for prostate cancer research in southern Africa, but also the benefits that genomic medicine would offer all peoples, recollected Professor Hayes.

We hope this study is the first step to that realization.

References:

African-specific molecular taxonomy of prostate cancer by Weerachai Jaratlerdsiri, Jue Jiang, Tingting Gong, Sean M. Patrick, Cali Willet, Tracy Chew, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Melanie Louw, James G. Kench, Raymond Campbell, Lisa G. Horvath, Eva K. F. Chan, David C. Wedge, Rosemarie Sadsad, Ilma Simoni Brum, Shingai B. A. Mutambirwa, Phillip D. Stricker, M. S. Riana Bornman, and Vanessa M. Hayes, 31 August 2022, Nature.DOI: 10.1038/s41586-022-05154-6

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers by Tingting Gong, Weerachai Jaratlerdsiri, Jue Jiang, Cali Willet, Tracy Chew, Sean M. Patrick, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Ilma Simoni Brum, Phillip D. Stricker, Shingai B. A. Mutambirwa, Rosemarie Sadsad, Anthony T. Papenfuss, Riana M. S. Bornman, Eva K. F. Chan and Vanessa M. Hayes, 31 August 2022, Genome Medicine.DOI: 10.1186/s13073-022-01096-w

Professor Hayes acknowledges the foresight of The Petre Foundation and donor Daniel Petre who has supported her vision for inclusive genomic research for over eight years.

Excerpt from:
Ancestral Heritage and Cancer: New Connection Discovered - SciTechDaily

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Complete the form below to unlock access to this Audio Article: "Unexpected Production of Cysteine Amino Acid Found in Coral "

From their use in basic biology to the development and testing of novel therapeutics, model organisms have helped to solve key scientific questions in experiments that are either impractical or unethical to conduct in humans. Important examples include rats, mice, zebrafish and non-human primates, often chosen for their likeness to humans in terms of anatomy, physiology or immunological response.

However, not all results gathered using model organisms can be translated to humans an acknowledged limitation of their use. A new genetic study of corals of the genus Acropora has emphasized this point further still, uncovering an unexpected pathway for the biosynthesis of an essential amino acid.

Cysteine (Cys) is an amino acid found in high abundance across many biological processes, such as protein synthesis and metabolism. In animals, the synthesis of cysteine was thought to occur via one specific pathway, known as the transsulfuration pathway, which involves the enzyme cystathionine -synthase (CBS) encoded by the CBS gene.

Researchers at the King Abdullah University of Science and Technology (KAUST) were studying corals of the Acroporoa genus, with the aim of generating a high-quality genome of Acropora loripes, a valuable genomic resource for future research. We werent searching for possible cysteine biosynthesis inAcropora, says Dr. Octavio Salazar, a postdoc in The Coral Symbiomics lab at KAUST, and lead author of the study.

And yet thats exactly what the researchers found; a surprise, considering that previous work had suggested the CBS gene had been lost in these corals, meaning they must rely on symbiotic relationships with algae to receive cysteine.

Once the genome was complete, Salazar and colleagues searched for proof that the CBS gene was in fact absent. It was, but Salazar remained skeptical.

I started searching the genome for genes encoding for enzymes that looked similar to those in other known cysteine biosynthesis pathways, such as those found in fungi and bacteria, says Salazar. I was quite surprised to find two enzymes in the coral with similarities to a recently identified alternative cysteine biosynthesis pathway in fungi.

The research team used yeast mutants that are completely unable to synthesize cysteine, and inserted the genes found in Acropora. Interestingly, the mutant yeast began to produce cysteine, indicating that the enzymes encoded by the genes found in the coral could synthesize the amino acid in vivo.

When looking further afield in the genomic landscape, Salazar and colleagues found that the genes were also present in the genomes of all animal phyla, except for vertebrates, nematodes and arthropods. As these three groups are the source of the most common model organisms used in scientific research, the team advise caution when it comes to overlying on findings from animal models.

This study proves the value of keeping an open mind when it comes to studying living creatures, says principal investigator Professor Manuel Aranda from KAUST. Sometimes knowledge can put you in a box; if you analyze data using only what you think you know, you may well miss something. OurAcroporagenome will be hugely valuable for future studies and who knows, it could reveal other unexpected details along the way.

Reference: Salazar OR, N. Arun P, Cui G, et al. The coral Acropora loripes genome reveals an alternative pathway for cysteine biosynthesis in animals. Sci Adv. 2022 8(38):eabq0304. doi:10.1126/sciadv.abq0304.

This article is a rework of a press release issued by KAUST university. Material has been edited for length and content.

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Unexpected Production of Cysteine Amino Acid Found in Coral - Technology Networks