Article
Oncology
Vaidehi Jobanputra, Kazimierz O. Wrzeszczynski, Reinhard Buttner, Carlos Caldas, Edwin Cuppen, Sean Grimmond, Torsten Haferlach, Charles Mullighan, Anna Schuh, Olivier Elemento
Summary: Whole-genome and transcriptome sequencing (WGTS) provides new opportunities for identifying and reporting a larger number of potentially actionable alterations in clinical tumor samples. However, these comprehensive tests also come with challenges such as the extent and diversity of sequence alterations and the complexity of interpretation.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Andrew M. Glazer, Giovanni Davogustto, Christian M. Shaffer, Carlos G. Vanoye, Reshma R. Desai, Eric H. Farber-Eger, Ozan Dikilitas, Ning Shang, Jennifer A. Pacheco, Tao Yang, Ayesha Muhammad, Jonathan D. Mosley, Sara L. Van Driest, Quinn S. Wells, Lauren Lee Shaffer, Olivia R. Kalash, Yuko Wada, Sarah Bland, Zachary T. Yoneda, Devyn W. Mitchell, Brett M. Kroncke, Iftikhar J. Kullo, Gail P. Jarvik, Adam S. Gordon, Eric B. Larson, Teri A. Manolio, Tooraj Mirshahi, Jonathan Z. Luo, Daniel Schaid, Bahram Namjou, Tarek Alsaied, Rajbir Singh, Ashutosh Singhal, Cong Liu, Chunhua Weng, George Hripcsak, James D. Ralston, Elizabeth M. McNally, Wendy K. Chung, David S. Carrell, Kathleen A. Leppig, Hakon Hakonarson, Patrick Sleiman, Sunghwan Sohn, Joseph Glessner, Joshua Denny, Wei-Qi Wei, Alfred L. George, M. Benjamin Shoemaker, Dan M. Roden
Summary: This study sequenced Mendelian arrhythmia genes in a large population without indication for arrhythmia genetic testing, identifying carriers of pathogenic or likely pathogenic variants. The study found that these variants were associated with higher burden of arrhythmia phenotypes and led to new diagnoses in some cases. By integrating genomic screening, electronic health record phenotypes, and in vitro functional studies, the disease risk from rare variants in arrhythmia genes can be assessed.
Article
Clinical Neurology
Alessio Di Fonzo, Marco Percetti, Edoardo Monfrini, Ilaria Palmieri, Alberto Albanese, Micol Avenali, Anna Bartoletti-Stella, Fabio Blandini, Gloria Brescia, Giovanna Calandra-Buonaura, Rosa Campopiano, Sabina Capellari, Isabel Colangelo, Giacomo Pietro Comi, Giada Cuconato, Rosangela Ferese, Caterina Galandra, Stefano Gambardella, Barbara Garavaglia, Andrea Gaudio, Emiliano Giardina, Federica Invernizzi, Paola Mandich, Rossana Mineri, Celeste Panteghini, Chiara Reale, Lucia Trevisan, Stefania Zampatti, Pietro Cortelli, Enza Maria Valente
Summary: This study attempts to harmonize the reporting of PD genetic testing across multiple diagnostic labs and highlights the current challenges in interpreting genetic variants from NGS-multigene panels, which has significant implications for counseling.
MOVEMENT DISORDERS
(2023)
Article
Genetics & Heredity
Dmitrii Smirnov, Lea D. Schlieben, Fatemeh Peymani, Riccardo Berutti, Holger Prokisch
Summary: RNA sequencing (RNA-seq) has become an increasingly applied and effective approach in molecular diagnostics, providing complementary information to DNA sequencing. It has been shown to enhance diagnostic rates by about 15% over whole-exome sequencing by detecting aberrant RNA phenotypes associated with pathogenic variants. However, there is currently no consensus on assessing variant pathogenicity strength based on RNA phenotypes. This study aims to evaluate the value of statistical significance and effect size of RNA phenotypes as evidence for variant pathogenicity and establish recommendations for integrating RNA-seq data into classification systems for molecular diagnostics.
Article
Medicine, General & Internal
Damian T. Rieke, Till de Bortoli, Peter Horak, Mario Lamping, Manuela Benary, Ivan Jelas, Gina Rueter, Johannes Berger, Marit Zettwitz, Niklas Kagelmann, Andreas Kind, Falk Fabian, Dieter Beule, Hanno Glimm, Benedikt Brors, Albrecht Stenzinger, Stefan Froehling, Ulrich Keilholz
Summary: The study compared the clinical interpretation of WES and RNA-Seq data by two independent molecular tumor boards, finding that reproducible clinical interpretation of high-dimensional molecular data is feasible. Challenges still exist in interpreting molecular aberrations beyond single nucleotide variants, clinically validated biomarkers, and combination therapies.
Article
Genetics & Heredity
Jodell E. Linder, Aimee Allworth, Sarah T. Bland, Pedro J. Caraballo, Rex L. Chisholm, Ellen Wright Clayton, David R. Crosslin, Ozan Dikilitas, Alanna DiVietro, Edward D. Esplin, Sophie Forman, Robert R. Freimuth, Adam S. Gordon, Richard Green, Maegan Harden, Ingrid A. Holm, Gail P. Jarvik, Elizabeth W. Karlson, Sofia Labrecque, Niall J. Lennon, Nita A. Limdi, Kathleen F. Mittendorf, Shawn N. Murphy, Lori Orlando, Cynthia A. Prows, Luke Rasmussen, Laura Rasmussen-Torvik, Robb Rowley, Konrad Teodor Sawicki, Tara Schmidlen, Shannon Terek, David Veenstra, Digna R. Velez Edwards, Devin Absher, Noura S. Abul-Husn, Jorge Alsip, Hana Bangash, Mark Beasley, Jennifer E. Below, Eta S. Berner, James Booth, Wendy K. Chung, James J. Cimino, John Connolly, Patrick Davis, Beth Devine, Stephanie M. Fullerton, Candace Guiducci, Melissa L. Habrat, Heather Hain, Hakon Hakonarson, Margaret Harr, Eden Haverfield, Valentina Hernandez, Christin Hoell, Martha Horike-Pyne, George Hripcsak, Marguerite R. Irvin, Christopher Kachulis, Dean Karavite, Eimear E. Kenny, Atlas Khan, Krzysztof Kiryluk, Bruce Korf, Leah Kottyan, Iftikhar J. Kullo, Katie Larkin, Cong Liu, Edyta Malolepsza, Teri A. Manolio, Thomas May, Elizabeth M. McNally, Frank Mentch, Alexandra Miller, Sean D. Mooney, Priyanka Murali, Brenda Mutai, Naveen Muthu, Bahram Namjou, Emma F. Perez, Megan J. Puckelwartz, Tejinder Rakhra-Burris, Dan M. Roden, Elisabeth A. Rosenthal, Seyedmohammad Saadatagah, Maya Sabatello, Dan J. Schaid, Baergen Schultz, Lynn Seabolt, Gabriel Q. Shaibi, Richard R. Sharp, Brian Shirts, Maureen E. Smith, Jordan W. Smoller, Rene Sterling, Sabrina A. Suckiel, Jeritt Thayer, Hemant K. Tiwari, Susan B. Trinidad, Theresa Walunas, Wei-Qi Wei, Quinn S. Wells, Chunhua Weng, Georgia L. Wiesner, Ken Wiley, Josh F. eMERGE Consortium, Josh F. Peterson
Summary: To assess the risk of common, complex diseases, it is important to consider clinical risk factors as well as monogenic and polygenic risks, which can be reflected in family history. Returning risk information to individuals and providers can impact preventive healthcare and the use of prophylactic therapies for those at high genetic risk.
GENETICS IN MEDICINE
(2023)
Review
Biochemical Research Methods
Dohun Yi, Jin-Wu Nam, Hyobin Jeong
Summary: Structural variants (SVs) are diverse genomic rearrangements that accumulate in the genome during cell development and aging, potentially impacting cancer development. Detecting somatic SVs is challenging but crucial for understanding their functional implications. This review summarizes recent advances in whole-genome sequencing (WGS)-based approaches for somatic SV detection, including computational algorithms for bulk WGS data and cutting-edge single-cell techniques. The advantages and limitations of bulk and single-cell approaches are discussed, along with their potential for linking somatic SVs to functional readouts.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Oncology
Alexander Mustea, Damian J. Ralser, Eva Egger, Ulrike Ziehm, Sonia Vivas, Stephan Brock, David Jackson, Mateja Condic, Christian Meisel, Lucia Otten, Anna Laib, Miguel Cubas Cordova, Rahel Hartmann, Martin A. Stein, Dominique Koensgen, Matthias B. Stope
Summary: This study successfully determined the four TCGA EC molecular subtypes using a single-method whole-exome sequencing approach provided by MH Guide, and compared their prognostic value with the TCGA classification. The results showed high concordance between the two approaches in terms of prognostic significance. This suggests that the MH Guide approach can reliably reproduce the multi-method-based TCGA EC molecular subtypes and represents a promising diagnostic tool.
Article
Chemistry, Multidisciplinary
Nicola Capuano, Pasquale Foggia, Luca Greco, Pierluigi Ritrovato
Summary: This study proposes a linked data approach based on multilayer networks and semantic Web standards to integrate and harmonize multiple biomedical datasets with different schemas and semi-structured data, addressing the challenge of heterogeneous data formats.
APPLIED SCIENCES-BASEL
(2022)
Article
Biotechnology & Applied Microbiology
Ratanond Koonchanok, Swapna Vidhur Daulatabad, Quoseena Mir, Khairi Reda, Sarath Chandra Janga
Summary: Sequoia is a visual analytics tool that allows interactive exploration of nanopore sequences, enabling detection of post-transcriptional modifications at a single-molecule resolution for building automated classifiers. Insights gleaned through visual analysis should aid in developing rationales, hypotheses, and insights into the dynamic nature of RNA.
Article
Engineering, Multidisciplinary
Li Zou, Xiu-Xiu Zhan, Jie Sun, Alan Hanjalic, Huijuan Wang
Summary: This study focuses on predicting temporal networks using interpretable learning algorithms like Lasso Regression and Random Forest. The results show that the next step activity of a particular link is mainly influenced by its current activity and links strongly correlated in the time series and close in distance in the aggregated network.
IEEE TRANSACTIONS ON NETWORK SCIENCE AND ENGINEERING
(2022)
Review
Oncology
Jordi Badia-Ramentol, Francisco Gimeno-Valiente, Elena Durendez, Carolina Martinez-Ciarpaglini, Jenniffer Linares, Mar Iglesias, Andres Cervantes, Alexandre Calon, Noelia Tarazona
Summary: Adjuvant chemotherapy is the main treatment option for localized colorectal cancer (CRC), but many patients have unfavorable outcomes. CDX2, a biomarker of prognosis and relapse, is associated with the complexity of CRC. Immunohistochemistry evaluation of CDX2 can identify high-risk CRC patients, but assessing its expression remains challenging in many patients.
CANCER TREATMENT REVIEWS
(2023)
Review
Chemistry, Multidisciplinary
Xiaocen Lu, Kristen Y. S. Kong, Peter J. Unrau
Summary: The field of fluorogenic RNA aptamers aims to overcome the lack of naturally fluorescent RNA molecules by developing small RNA tags that can bind to fluorogenic ligands and enhance fluorescence. Various mechanisms of fluorogenicity have been discovered in the past decade, resulting in over seventy aptamer:ligand pairs with high molar brightness and binding affinity. This review discusses selection methods, provides guidelines for choosing fluorescent RNA tools, and highlights the importance of global standards for evaluating these systems.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Oncology
Xiaoyu He, Yu Zhang, Danyang Yuan, Xinyin Han, Jiayin He, Xiaohong Duan, Siyao Liu, Xintong Wang, Beifang Niu
Summary: NGS technology has greatly advanced human cancer research, but limitations exist in the clinical application. The introduction of GPyFlow and DIVIS tools effectively facilitate complex cancer genome sequencing analyses.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Benjamin Crysup, August E. Woerner, Jonathan L. King, Bruce Budowle
Summary: Genetic methods are expanding, transitioning from forensic genetic assays limited to tens of loci to forensic genomic approaches that can assess thousands to millions of loci. Subtle distinctions between genetic assays and their genomic counterparts can impact forensic match statistics. A graph algorithm is described in the study to assess forensic match statistics on mitochondrial DNA mixtures in a way that is invariant to variant calling conventions and alignment parameters.
Article
Urology & Nephrology
Miguel Verbitsky, Sarathbabu Krishnamurthy, Priya Krithivasan, Daniel Hughes, Atlas Khan, Maddalena Marasa, Natalie Vena, Pavan Khosla, Junying Zhang, Tze Y. Lim, Joseph T. Glessner, Chunhua Weng, Ning Shang, Yufeng Shen, George Hripcsak, Hakon Hakonarson, Iuliana Ionita-Laza, Brynn Levy, Eimear E. Kenny, Ruth J. F. Loos, Krzysztof Kiryluk, Simone Sanna-Cherchi, David R. Crosslin, Susan Furth, Bradley A. Warady, Robert P. Igo Jr, Sudha K. Iyengar, Craig S. Wong, Afshin Parsa, Harold I. Feldman, Ali G. Gharavi
Summary: The prevalence of genomic disorders (GDs) was higher in patients with chronic kidney disease (CKD) compared to controls. Children with CKD had a higher rate of GDs (3.6%) compared to adults with CKD (1.1%). GDs were associated with comorbidities such as diabetes and neuropsychiatric symptoms.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Suresh C. C. Tyagi, Sathnur Pushpakumar, Utpal Sen, Sri Prakash L. Mokshagundam, Dinesh K. K. Kalra, Mohamed A. A. Saad, Mahavir Singh
Summary: Although the mechanisms underlying respiratory failure in Duchenne muscular dystrophy (DMD) and long-COVID are unclear, there is evidence of neopterin (NPT) involvement in both conditions. Studies have shown increased levels of NPT and other inflammatory markers in lung tissue, leading to fibrosis of the diaphragm. Understanding the epigenetic regulation and generation of NPT in long-COVID patients is of interest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Carrie L. Blout Zawatsky, David Bick, Louise Bier, Birgit Funke, Matthew Lebo, Katie L. Lewis, Ekaterina Orlova, Emily Qian, Lauren Ryan, Marci L. B. Schwartz, Emily R. Soper
Summary: Genetic counseling for elective genomic testing (EGT) is becoming more common, which has the potential to detect genetic conditions before significant health impact. Pre- and post-test counseling for EGT require complete family and medical history, but there are special considerations due to uncertainties and lack of guidelines. This practice resource aims to provide guidance for genetic counselors and healthcare providers caring for adults seeking EGT counseling.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Multidisciplinary Sciences
Konrad Teodor Sawicki, Drew R. Nannini, Suzette J. Bielinski, Nicholas B. Larson, Donald M. Lloyd-Jones, Bruce Psaty, Kent D. Taylor, Sanjiv J. Shah, Laura J. Rasmussen-Torvik, John T. Wilkins, Elizabeth M. McNally, Ravi B. Patel
Summary: Circulating protease inhibitors play a critical role in regulating inflammation and are related to the development of heart failure (HF). In this study, the researchers investigated the association between circulating secretory leukocyte protease inhibitor (SLPI) and incident HF in a multi-ethnic cohort. The results showed that higher baseline serum SLPI levels were independently associated with incident HF and HFpEF, but not HFrEF, over long-term follow-up. This suggests that serum SLPI may be a biomarker for inflammation and provides insights into the pathobiology of HFpEF.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Elizabeth M. McNally, Karisma R. Chhabria, Dominic E. Fullenkamp
CIRCULATION-HEART FAILURE
(2023)
Article
Genetics & Heredity
Hila Milo Rasouly, Olivia Balderes, Maddalena Marasa, Hilda Fernandez, Marissa Lipton, Fangming Lin, Ali G. Gharavi, Maya Sabatello
Summary: The success of genomic medicine depends on integrating genetic knowledge into clinical practices. However, the referral of patients to genetic evaluation or testing by clinicians may be limited by their knowledge in genetics. A survey was conducted among nephrologists in the United States, revealing that a significant proportion of nephrologists have limited genetic knowledge, and there is a need to enhance their genetic education to promote the use of genetic testing in nephrology.
GENETICS IN MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Aangi J. Shah, Taylor Beckmann, Mounica Vorla, Dinesh K. Kalra
Summary: Pulmonary arterial hypertension (PAH) is a chronic and progressive disorder that affects the pulmonary vasculature and leads to pulmonary and cardiac remodeling. Despite improved life expectancy through targeted therapies, PAH still remains a progressive disease with significant morbidity and mortality. Current vasodilator therapies do not target the underlying pathogenesis of the disease, highlighting the need for the development of new drugs and interventional therapies. This review focuses on newer targets, drugs, and interventional therapies that modify various pathways involved in the pathogenesis of PAH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sathnur Pushpakumar, Mahavir Singh, Yuting Zheng, Oluwaseun E. Akinterinwa, Sri Prakash L. Mokshagundam, Utpal Sen, Dinesh K. Kalra, Suresh C. Tyagi
Summary: Renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF) but it is unclear whether RDN preserves ejection fraction (EF) during HFpEF. By creating an aorta-vena cava fistula (AVF) in mice, this study demonstrated that RDN is cardioprotective during HFpEF via preservation of eNOS and endocardial-endothelial function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Matthew B. Rich, Carrie Blout L. Zawatsky, Joseph J. Botta, Kurt D. Christensen
Summary: Our research examined how personal risk for AD may influence intentions to ask for medications to delay symptoms of AD, and how the availability of such medications impacts interest in AD-related genetic testing. Data from 310 individuals were analyzed. Findings suggest that individuals who know they have an increased risk for AD are more likely pursue medications to delay onset of disease symptoms, and the availability of AD-delaying treatments will increase interest in associated genetic testing.
JOURNAL OF GENETIC COUNSELING
(2023)
Review
Genetics & Heredity
Anna S. E. Cuomo, Aparna Nathan, Soumya Raychaudhuri, Daniel G. MacArthur, Joseph E. Powell
Summary: In this Review, the authors discuss the field of single-cell genetics, which combines single-cell genomics with human genetics. They highlight the importance of single-cell expression quantitative trait loci studies in linking genetic variation to cellular processes in human biology and disease. The authors also mention the potential implications of this field for disease diagnosis, risk prediction, and therapeutic development, and emphasize the need for advances in data generation and analysis methods to fully utilize single-cell genomic data.
NATURE REVIEWS GENETICS
(2023)
Article
Multidisciplinary Sciences
Yoonjung Yoonie Joo, Jennifer A. Pacheco, William K. Thompson, Laura J. Rasmussen-Torvik, Luke V. Rasmussen, Frederick T. J. Lin, Mariza de Andrade, Kenneth M. Borthwick, Erwin Bottinger, Andrew Cagan, David S. Carrell, Joshua C. Denny, Stephen B. Ellis, Omri Gottesman, James G. Linneman, Jyotishman Pathak, Peggy L. Peissig, Ning Shang, Gerard Tromp, Annapoorani Veerappan, Maureen E. Smith, Rex L. Chisholm, Andrew J. Gawron, M. Geoffrey Hayes, Abel N. Kho
Summary: We identified genetic risk variants and clinical phenotypes associated with diverticular disease (DD) using NLP and multiple EHR data sources. Our algorithm improved patient classification for DD analysis and replicated known associations between ARHGAP15 loci and DD. Additionally, we found significant associations between DD GWAS variants and circulatory system, genitourinary, and neoplastic EHR phenotypes.
Article
Cardiac & Cardiovascular Systems
Brenda Xiao, Digna Velez R. Edwards, Anastasia Lucas, Theodore Drivas, Kathryn Gray, Brendan Keating, Chunhua Weng, Gail P. Jarvik, Hakon Hakonarson, Leah Kottyan, Noemie Elhadad, Wei-Qi Wei, Yuan Luo, Dokyoon Kim, Marylyn Ritchie, Shefali Setia Verma
Summary: This study aimed to investigate the genetic overlap and impact of cardiometabolic traits on female-specific health conditions. The results showed that there is a significant association between cardiometabolic polygenic scores and certain female-specific health conditions.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Cardiac & Cardiovascular Systems
Dinesh K. Kalra, Mounica Vorla, Erin D. Michos, Anandita Agarwala, Salim Virani, Bart Duell, Frederick J. Raal
Summary: With the improvement of antiretroviral therapy, the life expectancy of people living with HIV has increased, but cardiovascular disease has become a major cause of morbidity and mortality in this aging population. Therefore, it is crucial to assess and treat cardiovascular disease risk factors, including dyslipidemia, in this population. However, there is limited evidence regarding the pathogenesis and management of dyslipidemia in people living with HIV.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Editorial Material
Medicine, General & Internal
U. Sagheer, M. K. Shotwell, M. Umer, W. Furtado, J. Joshi, D. K. Kalra
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2023)
Review
Genetics & Heredity
Samuel J. Virolainen, Andrew VonHandorf, Kenyatta C. M. F. Viel, Matthew T. Weirauch, Leah C. Kottyan
Summary: The molecular processes underlying human health and disease are highly complex, often involving non-additive gene-environment interactions. This work reviews the current knowledge on the impact of gene-environment interactions on human health, including the independent effects of genetic variation and the environment, as well as well-established interactions involving toxicants, pollution, viruses, and sex chromosome composition. The study concludes by discussing the possibilities and challenges in studying gene-environment interactions.
GENES AND IMMUNITY
(2023)