Sequencing the unknown made easy: Metaplatanus improves metagenome assembly

Metagenomics often involves sequencing DNA samples that can only be described as “tricky.” Such DNA shows high heterogeneity, which can cause interspecies misassemblies. These misassemblies threaten the very purpose of metagenome sequencing, which is to comprehensively study the gene pool, by generating multiple draft genomes in a given sample. This issue is further complicated by the presence of certain organisms in these samples that cannot be cultured using standard microbiology techniques. How can this cascade of issues be resolved?
Scientists from Tokyo Tech now have the answer. They have developed a novel metagenome assembler called MetaPlatanus, which can generate accurate DNA sequences, including those of uncultured organisms. Their breakthrough findings have been published as a research article in Nucleic Acids Research.
MetaPlatanus uses accurate short DNA sequence reads to assemble contigs. Contigs are slightly longer stretches of DNA sequence that are analogous to jigsaw puzzle pieces in the larger genome. The contigs are assembled into larger chromosome-scale scaffolds by repeatedly using inputs like long-range sequence links, species-specific sequence compositions, coverage depth, and binning information.
Explaining the choice of inputs for MetaPlatanus-based scaffold generation, Dr. Rei Kajitani, Assistant Professor at the School of Life Science and Technology, Tokyo Tech, and the lead scientist of the study, says, “We employ a hybrid metagenome assembly method that not only utilizes the advantages of both short-range and long-range sequence reads, but also compensates for the shortcomings posed by either read lengths, and the sample itself.”
He further adds, “We have applied binning to link sequences divided by regions that are hard to assemble, such as repetitive ones. Our approach is novel since the combination of binning and assembly processes have not been implemented as a public tool, so far!”
Dr. Kajitani and his team left no stone unturned in checking the accuracy of results churned out by MetaPlatanus. In this regard, they performed a process called benchmarking using mock datasets of known bacteria. Not surprisingly, MetaPlatanus gave outputs that were highly contiguous, with very few interspecies misassemblies.
Notably, while testing MetaPlatanus’ accuracy with already published human gut data, it additionally assembled many biologically important elements, including coding genes, gene clusters, viral sequences, and over-half bacterial genomes.
Also, compared to other existing tools, only MetaPlatanus was able to perform near-complete assembly of some high-abundance bacterial genomes, while benchmarking using already published human saliva data.
Indeed, Dr. Kajitani and his team appear to have struck metagenomic gold with MetaPlatanus. Excited about the potential applications of MetaPlatanus, he exclaims, “We believe that the metagenome assembler that we have developed at Tokyo Tech could help examine the contexts of sequence elements spreading over the genome, which could have innumerable real-world applications.”
Undoubtedly, this study could prove to be a milestone in the field of metagenomics.
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Materials provided by Tokyo Institute of Technology. Note: Content may be edited for style and length.

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Excess deaths in people with mental health conditions increased during the COVID-19 pandemic

The greater number of deaths amongst those with mental health conditions and intellectual disabilities has been amplified during the COVID-19 pandemic, a study based on more than 160,000 patients has revealed.
Before the pandemic the rates of mortality in those with severe mental health conditions were already higher than the general population. New research published in The Lancet Regional Health — Europe shows that between March and June 2020, during the first wave of COVID-19, mortality further increased in people with mental health conditions and intellectual disabilities compared with the general population.
The study was published in the run up to World Mental Health Day on 10 October 2021 which this year has the theme ‘Mental Health in an Unequal World’.
Deaths from COVID-19 among those with learning disabilities were nine times higher than the general population during the first lockdown period, according to the study, and for those with eating disorders almost five times higher. For those with personality disorders and those with dementia, deaths from COVID-19 were about four times higher than the general population and more than three times higher in people with schizophrenia.
The research was part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC) and used the Clinical Record Interactive Search (CRIS) system to analyse anonymised data from clinical e-records of patients from South London.
Lead author Dr Jayati Das-Munshi, Reader in Social and Psychiatric Epidemiology at King’s College London and Honorary Consultant Psychiatrist with South London and Maudsley NHS Foundation Trust, said: “The results from our study paint a stark picture of how the existing vulnerability of those with mental health conditions and intellectual disabilities have worsened during the COVID-19 pandemic. The higher death rates compared to the general population were associated with more deaths from COVID-19 infection itself, as well as deaths from other causes.

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Using indoor air sampling surveillance to sniff out COVID-19

A team of scientists and doctors from the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) at Nanyang Technological University, Singapore (NTU Singapore) and the NUS Yong Loo Lin School of Medicine has developed a capability to detect airborne SARS-CoV-2 RNA — the nucleic acid coding for the virus that causes COVID-19 — indoors through air sampling.
When trialled in two inpatient wards of a major Singaporean hospital caring for active COVID-19 patients the air surveillance approach produced a higher detection rate of environmental SARS-CoV-2 RNA compared to surface swab samples collected in the same area.
The COVID-19 Delta variant’s rapid spread in Singapore and globally underlines the need for rapid identification of the presence of SARS-CoV-2 in the environment. While wastewater testing is a reliable indicator of the presence of virus in sewage discharge, the retrospective nature of this approach means pre-emptive action is not possible.
The findings, described in a study published in Indoor Air on 14 Sept, indicate the potential for an airborne surveillance system that monitors for the presence of the virus and provides early warning of infection risks, which would be especially valuable in hospitals and nursing homes, and in enclosed places where large numbers of people congregate, said the research team.
Professor Paul Tambyah, deputy director of NUS Medicine’s Infectious Diseases Translational Research Programme and President of Asia Pacific Society of Clinical Microbiology and Infection, said “The results of this air sampling study are encouraging, with the potential for the simple monitoring for the presence of COVID-19 in possible hotspots. This will allow for timely intervention where necessary to prevent the emergence of clusters. Hopefully this will prove useful as the country gradually transitions into recognising that the disease has become endemic and everyone learns to live as normally as possible with the virus.”
Dr Irvan Luhung, SCELSE senior research fellow and study co-lead author, said “This study demonstrated the versatility and sensitivity of air sampling for monitoring SARS-CoV-2 in hospital settings, something that was previously not thought possible due to the high ventilation rate of hospital wards. Such an air surveillance capability could make a valuable contribution towards keeping frontline medical staff safe in this pandemic. In hospitals with a high daily number of COVID-19 patients, employing a routine air surveillance programme with high sensitivity could be beneficial in detecting the virus early and help to keep frontline medical staff safe.”
Associate Professor David Allen from NUS Medicine’s Infectious Diseases Translational Research Programme and an infectious diseases clinician at the National University Health System (NUHS), said “The paper’s findings expand our knowledge of the extent to which the virus may potentially be transmitted in different types of wards — this impacts safety and needed precautions for health care workers. The findings also advance the potential use of different methods of detecting virus in the environment to provide additional tools for mass screening (other methods are screening each person, sampling sewage, etc) — in our case a device which samples the air for the presence of virus.”

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Stem cell population identified that is key for bone regeneration

Mesenchymal stem cells (MSCs) are thought to have great potential in the field of regenerative medicine, which has the aim of restoring damaged tissues. However, not much was known about in vivo plasticity of them — until now. Researchers have identified a subpopulation of MSCs that promote the healing of bone fractures and show an enhanced ability to differentiate into various cell types.
MSCs are found in bone marrow, and are “multipotent,” meaning that they can both renew themselves and develop into a variety of specialized cell types, such as bone, fat, and cartilage cells. The researchers had previously developed a mouse line that uses green fluorescent protein to highlight cells expressing a particular molecule known as CD73. Studies of the bone marrow in this mouse revealed that a subpopulation of MSCs expressed CD73, as well as the sinusoidal endothelial cells (sECs) that are part of the vascular system of the bone marrow.
The CD73-positive MSCs could be seen to proliferate more than the CD73- negative MSCs, and to have a higher potential to differentiate into different cell types, indicating that this group of MSCs may be particularly effective for bone repair. The researchers therefore went on to study the functions of these CD73-positive MSCs in fracture healing.
As a fracture heals, it progresses through various stages. These include clotted blood forming at the fracture, which becomes replaced by a callus of fibrous tissues and cartilage, followed by formation of a hard bony callus. The bone is then remodeled, as regular bone replaces the hard callus and the bone returns to its usual shape.
“The generation of the callus is critically dependent on the recruitment of MSCs from the surrounding tissue and the bone marrow,” explains lead author Assistant Professor Kenichi Kimura. “Therefore, fracture healing models are helpful for exploring the cellular dynamics of MSC migration and differentiation during tissue regeneration.”
The team was able to observe the CD73-positive MSCs moving towards the site of the fracture and forming new cartilage and bone cells to heal the fracture. The CD73-positive sECs were also involved in the healing of the fracture, as they contributed to the process of “neovascularization,” the formation of new blood vessels to support the healed bone.
Finally, they went on to graft CD73-positive MSCs into the area of a fracture, which markedly enhanced the healing process compared with when they grafted into CD73-negative MSCs.
Says Assistant Professor Kimura, “The identification of this subpopulation of MSCs could be of great benefit for regenerative medicine and the treatment of fractures.”
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Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

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Personalized medicine: Platform enables comparative research on cancerous tumors

Researchers at the Technion’s Rappaport Faculty of Medicine have developed an innovative algorithm that detects an uninterrupted common denominator in multidimensional data gathered from tumors of different patients. The study, which was published in Cell Systems, was led by Professor Shai Shen-Orr, Dr. Yishai Ofran, and Dr. Ayelet Alpert, and conducted in collaboration between researchers at the Technion, the Rambam Health Care Campus, the Shaare Zedek Medical Center and the University of Texas.
In recent years, cancer research has undergone a series of significant revolutions, including the introduction of single-cell high-resolution characterization capabilities, or, more specifically, simultaneous high-throughput profiling of cancer samples using single-cell RNA sequencing and proteomics analysis. This has led to the generation of vast quantities of multidimensional data on a huge number of cells, allowing for the characterization of both the healthy tissue and malignant tissues. This high amount of data has revealed the great variability between tumors of different patients, where cellular characterization that is derived from the patient’s genetic background is unique to each patient.
Despite the substantial advantage that is derived from such an accurate characterization of the specific patient, this development hinders comparison of different patients: in the absence of a common denominator, the comparison, which is essential for identifying prognostic markers (e.g. mortality or severity of illness), becomes impossible.
The tuMap algorithm developed by the Technion researchers provides a solution to this complex challenge by means of a “variance-based comparison.” The innovative algorithm delivers the possibility to place numerous different tumors on a uniform scale that provides a benchmark for comparison. In this way, the tumors of different patients can be meaningfully compared, as well as tumors of the same patient over the disease course (for example, on diagnosis and after treatment). The resolution provided by the algorithm can be leveraged for clinical applications such as prediction of various clinical indices with a very high accuracy, outperforming traditional tools. Although the researchers tested the algorithm on leukemia tumors, they believe that it will also be relevant for other cancer types.
The research was sponsored by the Israel Science Foundation, the Rappaport Family Institute for Research in the Medical Sciences, and the National Institutes of Health (NIH).
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Materials provided by Technion-Israel Institute of Technology. Note: Content may be edited for style and length.

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What makes us human? The answer may be found in overlooked DNA

Our DNA is very similar to that of the chimpanzee, which in evolutionary terms is our closest living relative. Stem cell researchers at Lund University in Sweden have now found a previously overlooked part of our DNA, so-called non-coded DNA, that appears to contribute to a difference which, despite all our similarities, may explain why our brains work differently. The study is published in the journal Cell Stem Cell.
The chimpanzee is our closest living relative in evolutionary terms and research suggests our kinship derives from a common ancestor. About five to six million years ago, our evolutionary paths separated, leading to the chimpanzee of today, and Homo Sapiens, humankind in the 21st century.
In a new study, stem cell researchers at Lund examined what it is in our DNA that makes human and chimpanzee brains different — and they have found answers.
“Instead of studying living humans and chimpanzees, we used stem cells grown in a lab. The stem cells were reprogrammed from skin cells by our partners in Germany, the USA and Japan. Then we examined the stem cells that we had developed into brain cells,” explains Johan Jakobsson, professor of neuroscience at Lund University, who led the study.
Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers then found that humans and chimpanzees use a part of their DNA in different ways, which appears to play a considerable role in the development of our brains.
“The part of our DNA identified as different was unexpected. It was a so-called structural variant of DNA that were previously called “junk DNA,” a long repetitive DNA string which has long been deemed to have no function. Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are — which only makes up about two per cent of our entire DNA — and examined the proteins themselves to find examples of differences.”
The new findings thus indicate that the differences appear to lie outside the protein-coding genes in what has been labelled as “junk DNA,” which was thought to have no function and which constitutes the majority of our DNA.

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Psychiatric disorders in teenage years associated with social exclusion in later life

Adolescents who had received a mental health disorder diagnosis were often excluded from the labour market and education as young adults. This particularly applied to adolescents who had been diagnosed with an autism spectrum disorder or psychosis. The results were found out in a birth cohort study of people born in Finland in 1987. The study was published on 6 October in British Journal of Psychiatry.
Almost eleven percent of adolescents who had received a psychiatric diagnosis were excluded from education and labour market for at least five years in their early adulthood. For other adolescents, this number was slightly under three percent. The results highlight the importance of the treatment and rehabilitation of people with mental health disorders in the prevention of adolescents’ social exclusion. ”
“To help prevent the social exclusion of adolescents, their treatment and rehabilitation require more resources than are currently being used as well as development of evidence-based treatment and rehabilitation,” says Adolescent Psychiatrist and Doctoral Candidate Ida Ringbom from the Research Centre for Child Psychiatry at the University of Turku.
The results are concerning because they highlight the link between mental health disorders and long-term exclusion from education and labour market. In the study, long-term exclusion was defined as a period spent outside education or paid employment lasting a minimum of five years. The link was particularly strong with those teenagers who had not completed their upper secondary education and who had been diagnosed with a mental health disorder. Almost half of these teenagers who had experienced psychosis and almost three quarters of teenagers who had been diagnosed with an autism spectrum disorder experienced long-term exclusion from education and labour market in their early adulthood.
“Vocational rehabilitation and tight collaboration between psychiatry and social services are important for enabling adolescents suffering from mental health problems to access the labour market,” says Assistant Professor David Gyllenberg who led the study.
“Adolescents who have not completed their upper secondary education require more targeted support because their risk of becoming socially excluded is particularly high.”
The research was conducted at the Research Centre for Child Psychiatry as a part of the INVEST flagship programme for the study of inequality, interventions, and the welfare state. A joint project of the University of Turku and Finnish Institute for Health and Welfare and funded by the Academy of Finland, INVEST focuses on reducing social inequality and reforming the welfare state. Finnish Institute for Health and Welfare is responsible for the national birth cohort of 1987. The research group included researchers from e.g. the University of Turku, Finnish Institute for Health and Welfare, Helsinki University Hospital, and Itla Children’s Foundation.
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Materials provided by University of Turku. Note: Content may be edited for style and length.

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Researcher investigates ways to enhance neurolysin activity in the brain

Ischemic stroke, the second leading cause of death worldwide, occurs when a vessel to the brain is blocked, reducing blood flow to the brain and depriving it of critical supplies of oxygen and nutrients. This process leads to the death of brain cells and leaves the patient with a sudden loss of certain body functions.
Tissue plasminogen activator, also known as tPA, is the lone pharmacological treatment for stroke, and while it is considered to be highly effective, it comes with one important, and often hard-to-meet caveat: it must be administered to the patient within 3-5 hours of stroke onset. Though many other significant efforts have been undertaken to discover and develop new drugs, there have been no new therapeutics approved to treat stroke since tPA was approved in 1996.
However, some recent advances in understanding signaling pathways that are relevant to the brain’s self-protective mechanisms have allowed investigators to identify novel targets for further study. One of those investigators, Vardan Karamyan, Ph.D., from the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy, has researched and collaborated with others to develop an effective treatment for stroke that focuses on the use of a peptidase known as neurolysin (Nln). Peptidases are enzymes that have the ability to cleave, or split peptides, which often leads to their inactivation.
Karamyan’s most recent collaborative study is a continuation of his previous work and evaluates the potential of Nln as a therapeutic target for stroke by seeking to identify small molecules capable of enhancing the activity and catalytic efficiency of Nln.
That study, “Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability,” was published Aug. 26 in the Journal of Medicinal Chemistry. Members of the Karamyan collaborative research team included Thomas J. Abbruscato, Ph.D., Andrew Baez, Shiva Hadi Esfahani, Pharm.D., Delaney Farris, Srinidhi Jayaraman, Ph.D., Nihar Kinarivala, Ph.D., Joanna Kocot, Ph.D., and Saeideh Nozohouri, Pharm.D., from TTUHSC; and Shikha Kumari, Ph.D., Md. Shafikur Rahman and Paul C. Trippier, Ph.D., from the University of Nebraska Medical Center. The project was supported by a grant from the National Institutes of Health.
In previous research, Karamyan’s lab first identified Nln as a key internal peptidase that helps protect the brain during acute neurodegenerative disorders such as stroke. His research showed that when Nln was inhibited after a stroke, there was more damage to the brain. However, when the amounts of Nln in the brain were increased prior to stroke, the damage was significantly reduced.

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Nerve repair, with help from stem cells

A new approach to repairing peripheral nerves marries the regenerating power of gingiva-derived mesenchymal stem cells with a biological scaffold to enable the functional recovery of nerves following a facial injury, according to a study by a cross-disciplinary team from the University of Pennsylvania School of Dental Medicine and Perelman School of Medicine.
Faced with repairing a major nerve injury to the face or mouth, skilled surgeons can take a nerve from an arm or leg and use to it restore movement or sensation to the original site of trauma. This approach, known as a nerve autograft, is the standard of care for nerve repair, but has its shortcomings. Besides taking a toll on a previously uninjured body part, the procedure doesn’t always result in complete and functional nerve regrowth, especially for larger injuries.
Scientists and clinicians have recently been employing a different strategy for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. In experimental approaches, these scaffolds are infused with growth factors and cells to support regeneration. But to date, these efforts have not been completely successful. Recovery can fall short due to a failure to coax large numbers of regenerating axons to cross the graft and then adequately mature and regrow myelin, the insulating material around peripheral nerves that allows them to fire quickly and efficiently.
In an innovative approach to guided nerve repair, shared in the journal npj Regenerative Medicine, the Penn team coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors. The current work demonstrated that infusing a scaffold with these cells and using them to guide the repair of facial nerve injuries in an animal model had the same effectiveness as an autograft procedure.
“Instead of an autograft, which causes unnecessary morbidity, we wanted to create a biological approach and use the regenerating ability of stem cells,” says Anh Le, senior author on the study and chair and a professor in the Department of Oral and Maxillofacial Surgery/Pharmacology in Penn’s School of Dental Medicine. “To be able to recreate nerve cells in this way is really a new paradigm.”
For more than a decade, Le’s lab has pioneered the use of GMSCs to treat several inflammatory diseases and to regrow a variety of types of craniofacial tissue. Gingival tissue is easily extracted and heals rapidly, offering an accessible source of GMSCs. In fact, gingival tissue is often discarded from routine dental procedures. Le says the potential of GMSCs to help in nerve regrowth also owes in part to the cells’ common lineage. “Embryologically, we know that craniofacial tissue is derived from the same neural crest progenitor cells as nerves,” Le says. “That’s part of the beauty of this system.”
Le and colleagues led by Qunzhou Zhang, now a faculty member at Penn Dental Medicine, were able to apply their previous understanding of GMSCs to grow them in a collagen matrix using specific conditions that encouraged the cells to grow more like Schwann cells, the cells’ identity confirmed with a variety of genetic markers.

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Baby-wearing products lead to higher risk of injury, hospitalizations in children under age 1

Baby-wearing products are an increasingly popular way to carry a young child in a sling, soft carrier or other type of device, but new research suggests that they can pose a higher risk of injury to children under age 1.
The study abstract, “Baby Wearing Injuries Presenting to Emergency Departments, 2011-2020: A Dangerous Fashion Trend,” — presented during the virtual American Academy of Pediatrics 2021 National Conference & Exhibition — shows that young children are not only more likely to sustain injury related to baby wearing but have a higher frequency of being hospitalized after the injury.
“The most precious thing a parent will ever wear is their child,” said author CPT Samantha Rowe, MD, MC, USA. “But like when buying a new pair of shoes, parents must be educated on the proper sizing, selection and wear of baby carriers to prevent injury to themselves and their child.”
Baby-wearing, also known as baby carrying, is a common form of attachment parenting that dates back to prehistoric times. Over the last decade, baby-wearing has demonstrated many benefits, including improved success with breastfeeding, improved infant to parent bonding, and improved attentiveness by fathers.
The researchers sought to characterize the epidemiology and impact of baby-wearing related injuries presenting to U.S. emergency departments. They reviewed 14,024 cases of baby-wearing injuries reported to the National Electronic Injury Surveillance System from 2011 to 2020 and found that 61% of children of injuries occurred in children aged 0-5 months with 19.3% of these infants requiring hospitalization, and 83.7% of these children injuring their heads. A total 18.1% of head injuries related to a baby-wearing product led to hospitalization.
More than one out of five — or 22% — of all injuries were associated with the caregiving falling. The authors found seven cases of cardiopulmonary arrest.
About 30% of baby-wearing injuries were associated with sling carriers, and 45% associated with non-specified types of baby carriers.
The authors suggest there is a need for more rigorous parental education regarding the use of baby carriers. They found a wide variety of products on the market, with most designed with additional space in the bust for breastfeeding women. This may increase the risk of injury to children when the product is worn by men.
Dr. Rowe will present the study abstract at Monday, Oct. 11, 2021.
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