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Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unkn … an other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun …

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unkn … an other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who hav …

Coordinated immune dysregulation in Juvenile Dermatomyositis revealed by single-cell genomics.

Juvenile Dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I interferon response and autoantibodies. Treatment options are limited due to incomplete understanding of how the disease emerges from dysregulated cell states across the immune system. We therefore investigated the blood of JDM patients at different stages of disease activity using single-cell transcriptomics paired with surface protein expression. By immunophenotyping peripheral blood mononuclear cells, we observed skewing of the B cell compartment towards an immature naive state as

Genomics driven precision oncology in advanced biliary tract cancer improves survival.

BACKGROUND: Biliary tract cancers (BTCs) including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are rare but aggressive malignancies with few effective standard of care therapies. METHODS: We implemented integrative clinical sequencing of advanced BTC tumors from 124 consecutive patients who progressed on standard therapies (N=92 with MI-ONCOSEQ and N=32 with commercial gene panels) enrolled between 2011-2020. RESULTS: Genomic profiling of paired tumor and normal DNA and tumor transcriptome (RNA) sequencing identified actionable somatic and germline g

Comparative genomics reveals the evolution of antimicrobial resistance in Bacteroides nordii.

Bacteroides nordii, is an understudied member of the pathogenic B. fragilis group which comprises several multidrug-resistant (MDR) strains. … nology. The draft genome was de-novo assembled and annotated, followed by comprehensive comparative genomics analyses using the publicly available genome dataset of B. nordii. The pan-genome analysis revealed the open nature of B. nordii, indicating the continuous accumulation of novel genes in non-core components leading to the emergence of new strains of …

Spatial genomics maps the structure, nature and evolution of cancer clones.

Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1-3. Although these are believed to aris … and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.

Digest: Population genomics reveals convergence toward melanism in different island populations.

Distinct traits between mainland and island populations provide an excellent opportunity to study the evolution and genetic basis of these traits. In this issue, Walsh et al. unraveled the evolution of black plumage color that arose independently in two island populations of the white-winged fairywren. They also described the first steps in understanding the genetic underpinnings of this trait.

Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterised by cognitive impairment, behavioural alteration, and functional decline. Over 130 AD-associated susceptibility loci have been identified by genome-wide association studies (GWAS), while whole genome sequencing (WGS) and whole exome sequencing (WES) studies have identified AD-associated rare variants. These variants are enriched in APOE, TREM2, CR1, CD33, CLU, BIN1, CD2AP, PILRA, SCIMP, PICALM, SORL1, SPI1, RIN3, and more genes. Given that aging is the single largest risk factor for late-onset AD (LOAD), the accumulat

Genomics of Smoldering Multiple Myeloma: Time for Clinical Translation of Findings?

Smoldering multiple myeloma (SMM) is an asymptomatic disorder of clonal bone marrow (BM) plasma cells (PCs) in between the premalignant condition known as monoclonal gammopathy of undetermined significance and overt multiple myeloma (MM). It is characterized by a deep biological heterogeneity that is reflected in a markedly variable progression risk among patients. Recently proposed risk stratification models mainly rely on indirect markers of disease burden and are unable to identify cases in whom clonal PCs have already undergone the "malignant switch" but major clonal expansion has not occu

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… Table 2 Prognostic models in SMM including biologic parameters (GEP, cytogenetics, genomics). … Whole genome sequencing of unique paired smm/mgus progressing to mm samples reveals a genomic landscape with diverse evolutionary pattern. Blood. 2016;128:2088. doi: 10.1182/blood.V128.22.2088.2088. 56. …

A genomics approach to females with infertility and recurrent pregnancy loss.

Infertility affects 10% of reproductive-age women and is extremely heterogeneous in etiology. The genetic contribution to female infertility is incompletely understood, and involves chromosomal and single-gene defects. Our aim in this study is to decipher single-gene causes in infertile women in whom endocrinological, anatomical, and chromosomal causes have been excluded. Our cohort comprises women with recurrent pregnancy loss and no offspring from spontaneous pregnancies (RPL, n = 61) and those who never achieved clinical pregnancy and were referred for in vitro fertilization [primary infert

Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. OBJECTIVES: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). METHODS: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant disco…

Experimental and bioinformatics considerations in cancer application of single cell genomics.

Single cell genomics offers an unprecedented resolution to interrogate genetic heterogeneity in a patient's tumour at the intercellular level. However, the DNA yield per cell is insufficient for today's sequencing library preparation protocols. This necessitates DNA amplification which is a key source of experimental noise. We provide an evaluation of two protocols using micro-fluidics based amplification for whole exome sequencing, which is an experimental scenario commonly used in single cell genomics. The results highlight their respective biases and relative strengths in identification of …

The Interaction of Genomics, Molecular Imaging, and Therapy in Gastrointestinal Tumors.

In the past 20 years there have been great advances in our understanding of the molecular genetics of gastrointestinal tumors. In general, c … umor occurrence, progression, and response to therapy. This chapter provides a brief summary of the genomics of gastrointestinal tumors, selected examples of targeted therapies, and examples of how current and emerging molecular imaging tools, assessing the tumor phenotype, inform our management of patients with tumors.

Using genomics to understand meticillin- and vancomycin-resistant Staphylococcus aureus infections.

Resistance to meticillin and vancomycin in Staphylococcus aureus significantly complicates the management of severe infections like bacteraemia, endocarditis or osteomyelitis. Here, we review the molecular mechanisms and genomic epidemiology of resistance to these agents, with a focus on how genomics has provided insights into the emergence and evolution of major meticillin-resistant S. aureus clones. We also provide insights on the use of bacterial whole-genome sequencing to inform management of S. aureus infections and for control of transmission at the hospital and in the community.

Multilevel genome typing: genomics-guided scalable resolution typing of microbial pathogens.

BackgroundBoth long- and short-term epidemiology are fundamental to disease control and require accurate bacterial typing. Genomic data resulting from implementation of whole genome sequencing in many public health laboratories can potentially provide highly sensitive and accurate descriptions of strain relatedness. Previous typing efforts using these data have mainly focussed on outbreak detection.AimWe aimed to develop multilevel genome typing (MGT), using consecutive multilocus sequence typing (MLST) schemes of increasing sizes, stepping up from seven-gene MLST to core genome MLST, to allow

The seventh pandemic of cholera in Europe revisited by microbial genomics.

In 1970, the seventh pandemic of cholera (7 P) reached both Africa and Europe. Between 1970 and 2011, several European countries reported cholera outbreaks of a few to more than 2,000 cases. We report here a whole-genome analysis of 1,324 7 P V. cholerae El Tor (7 PET) isolates, including 172 from autochthonous sporadic or outbreak cholera cases occurring between 1970 and 2011 in Europe, providing insight into the spatial and temporal spread of this pathogen across Europe. In this work, we show that the 7 PET lineage was introduced at least eight times into two main regions: Eastern and Southe

Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies.

Malignant pleural mesothelioma (MPM) is a rare, yet lethal asbestos-induced cancer and despite marked efforts to reduce occupational exposure, the incidence has not yet significantly declined. Since 2003, combined treatment with a platinum-based agent and pemetrexed has been the first-line therapy and no effective or approved second-line treatments have emerged. The seemingly slow advance in developing new MPM treatments does not appear to be related to a low level of clinical and pre-clinical research activity. Rather, we suggest that a key hurdle in successfully translating basic discovery i

Characterizing variants of unknown significance in rhodopsin: A functional genomics approach.

Characterizing the pathogenicity of DNA sequence variants of unknown significance (VUS) is a major bottleneck in human genetics, and is increasingly important in determining which patients with inherited retinal diseases could benefit from gene therapy. A library of 210 rhodopsin (RHO) variants from literature and in-house genetic diagnostic testing were created to efficiently detect pathogenic RHO variants that fail to express on the cell surface. This study, while focused on RHO, demonstrates a streamlined, generalizable method for detecting pathogenic VUS. A relatively simple next-generatio

Ethical dangers of facial phenotyping through photography in psychiatric genomics studies.

Psychiatric genomics research protocols are increasingly incorporating tools of deep phenotyping to observe and examine phenotypic abnormalities among individuals with neurodevelopmental disorders. In particular, photography and the use of two-dimensional and three-dimensional facial analysis is thought to shed further light on the phenotypic expression of the genes underlying neurodevelopmental disorders, as well as provide potential diagnostic tools for clinicians. In this paper, I argue that the research use of photography to aid facial phenotyping raises deeply fraught issues from an ethic…

Convergent functional genomics of cocaine misuse in humans and animal models.

Background: Data from the Global Burden of Disease Study 2016 recently estimated that after opioid and cannabis use disorders, cocaine use disorders were among the most common, with around 5.8 million cases around the world. Several genome-wide expression studies (GWES) for cocaine misuse have been carried out in brain tissues from patients and controls and in mouse and rat models.Objectives: In the current work, we used a convergent functional genomics approach to identify novel candidate genes and pathways for cocaine misuse.Methods: We carried out meta-analyses for available GWES for cocain…