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  1. Tumor mutational burden (TMB; the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as...

    Authors: Mary A. Wood, Benjamin R. Weeder, Julianne K. David, Abhinav Nellore and Reid F. Thompson

    Citation: Genome Medicine 2020 12:33

    Content type: Research

    Published on:

  2. Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of renal cancer. With currently available therapies, cure of advanced and metastatic ccRCC is achieved only in rare cases. Here, we developed a w...

    Authors: Anna Reustle, Moreno Di Marco, Carolin Meyerhoff, Annika Nelde, Juliane S. Walz, Stefan Winter, Siahei Kandabarau, Florian Büttner, Mathias Haag, Linus Backert, Daniel J. Kowalewski, Steffen Rausch, Jörg Hennenlotter, Viktoria Stühler, Marcus Scharpf, Falko Fend…

    Citation: Genome Medicine 2020 12:32

    Content type: Research

    Published on:

  3. Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin caused by either the integration of Merkel cell polyomavirus (MCPyV) and expression of viral T antigens or by ultraviolet...

    Authors: Gabriel J. Starrett, Manisha Thakuria, Tianqi Chen, Christina Marcelus, Jingwei Cheng, Jason Nomburg, Aaron R. Thorner, Michael K. Slevin, Winslow Powers, Robert T. Burns, Caitlin Perry, Adriano Piris, Frank C. Kuo, Guilherme Rabinowits, Anita Giobbie-Hurder, Laura E. MacConaill…

    Citation: Genome Medicine 2020 12:30

    Content type: Research

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  4. In cancer, normal epigenetic patterns are disturbed and contribute to gene expression changes, disease onset, and progression. The cancer epigenome is composed of the epigenetic patterns present in the tumor-i...

    Authors: Justyna A. Wierzbinska, Reka Toth, Naveed Ishaque, Karsten Rippe, Jan-Philipp Mallm, Lara C. Klett, Daniel Mertens, Thorsten Zenz, Thomas Hielscher, Marc Seifert, Ralf Küppers, Yassen Assenov, Pavlo Lutsik, Stephan Stilgenbauer, Philipp M. Roessner, Martina Seiffert…

    Citation: Genome Medicine 2020 12:29

    Content type: Research

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  5. Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous ge...

    Authors: Dennis Lal, Patrick May, Eduardo Perez-Palma, Kaitlin E. Samocha, Jack A. Kosmicki, Elise B. Robinson, Rikke S. Møller, Roland Krause, Peter Nürnberg, Sarah Weckhuysen, Peter De Jonghe, Renzo Guerrini, Lisa M. Niestroj, Juliana Du, Carla Marini, James S. Ware…

    Citation: Genome Medicine 2020 12:28

    Content type: Research

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  6. A comprehensive understanding of the pre-existing genetic variation in genes associated with antibiotic resistance in the Mycobacterium tuberculosis complex (MTBC) is needed to accurately interpret whole-genome s...

    Authors: Matthias Merker, Thomas A. Kohl, Ivan Barilar, Sönke Andres, Philip W. Fowler, Erja Chryssanthou, Kristian Ängeby, Pontus Jureen, Danesh Moradigaravand, Julian Parkhill, Sharon J. Peacock, Thomas Schön, Florian P. Maurer, Timothy Walker, Claudio Köser and Stefan Niemann

    Citation: Genome Medicine 2020 12:27

    Content type: Research

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  7. Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated...

    Authors: Simon Kebede Merid, Alexei Novoloaca, Gemma C. Sharp, Leanne K. Küpers, Alvin T. Kho, Ritu Roy, Lu Gao, Isabella Annesi-Maesano, Pooja Jain, Michelle Plusquin, Manolis Kogevinas, Catherine Allard, Florianne O. Vehmeijer, Nabila Kazmi, Lucas A. Salas, Faisal I. Rezwan…

    Citation: Genome Medicine 2020 12:25

    Content type: Research

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  8. Patient stratification based on molecular subtypes is an important strategy for cancer precision medicine. Deriving clinically informative cancer molecular subtypes from transcriptomic data generated on whole ...

    Authors: Li Wang, Robert P. Sebra, John P. Sfakianos, Kimaada Allette, Wenhui Wang, Seungyeul Yoo, Nina Bhardwaj, Eric E. Schadt, Xin Yao, Matthew D. Galsky and Jun Zhu

    Citation: Genome Medicine 2020 12:24

    Content type: Research

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  9. Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

    Authors: Christopher G. Smith, Tina Moser, Florent Mouliere, Johanna Field-Rayner, Matthew Eldridge, Anja L. Riediger, Dineika Chandrananda, Katrin Heider, Jonathan C. M. Wan, Anne Y. Warren, James Morris, Irena Hudecova, Wendy N. Cooper, Thomas J. Mitchell, Davina Gale, Andrea Ruiz-Valdepenas…

    Citation: Genome Medicine 2020 12:23

    Content type: Research

    Published on:

  10. T cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which suggests that inh...

    Authors: Kyungsoo Kim, Seyeon Park, Seong Yong Park, Gamin Kim, Su Myeong Park, Jae-Won Cho, Da Hee Kim, Young Min Park, Yoon Woo Koh, Hye Ryun Kim, Sang-Jun Ha and Insuk Lee

    Citation: Genome Medicine 2020 12:22

    Content type: Research

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  11. Despite growing numbers of immune checkpoint blockade (ICB) trials with available omics data, it remains challenging to evaluate the robustness of ICB response and immune evasion mechanisms comprehensively. To...

    Authors: Jingxin Fu, Karen Li, Wubing Zhang, Changxin Wan, Jing Zhang, Peng Jiang and X. Shirley Liu

    Citation: Genome Medicine 2020 12:21

    Content type: Database

    Published on:

  12. Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF...

    Authors: Qing Zhou, Samantha O. Perakis, Peter Ulz, Sumitra Mohan, Jakob M. Riedl, Emina Talakic, Sigurd Lax, Martin Tötsch, Gerald Hoefler, Thomas Bauernhofer, Martin Pichler, Armin Gerger, Jochen B. Geigl, Ellen Heitzer and Michael R. Speicher

    Citation: Genome Medicine 2020 12:20

    Content type: Research

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  13. Midbrain dopaminergic neurons (MDN) represent 0.0005% of the brain’s neuronal population and mediate cognition, food intake, and metabolism. MDN are also posited to underlay the neurobiological dysfunction of ...

    Authors: Sergio Espeso-Gil, Tobias Halene, Jaroslav Bendl, Bibi Kassim, Gabriella Ben Hutta, Marina Iskhakova, Neda Shokrian, Pavan Auluck, Behnam Javidfar, Prashanth Rajarajan, Sandhya Chandrasekaran, Cyril J. Peter, Alanna Cote, Rebecca Birnbaum, Will Liao, Tyler Borrman…

    Citation: Genome Medicine 2020 12:19

    Content type: Research

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  14. The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrast...

    Authors: F. M. Aarestrup, A. Albeyatti, W. J. Armitage, C. Auffray, L. Augello, R. Balling, N. Benhabiles, G. Bertolini, J. G. Bjaalie, M. Black, N. Blomberg, P. Bogaert, M. Bubak, B. Claerhout, L. Clarke, B. De Meulder…

    Citation: Genome Medicine 2020 12:18

    Content type: Opinion

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  15. Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. Howeve...

    Authors: Jason K. Sa, Jung Yong Hong, In-Kyoung Lee, Ju-sun Kim, Moon-Hee Sim, Ha Jung Kim, Ji Yeong An, Tae Sung Sohn, Joon Ho Lee, Jae Moon Bae, Sung Kim, Kyoung-Mee Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Ho Yeong Lim…

    Citation: Genome Medicine 2020 12:17

    Content type: Research

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  16. While clinical factors such as age, grade, stage, and histological subtype provide physicians with information about patient prognosis, genomic data can further improve these predictions. Previous studies have...

    Authors: Ajay Chatrath, Roza Przanowska, Shashi Kiran, Zhangli Su, Shekhar Saha, Briana Wilson, Takaaki Tsunematsu, Ji-Hye Ahn, Kyung Yong Lee, Teressa Paulsen, Ewelina Sobierajska, Manjari Kiran, Xiwei Tang, Tianxi Li, Pankaj Kumar, Aakrosh Ratan…

    Citation: Genome Medicine 2020 12:15

    Content type: Research

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  17. Exome sequencing (ES) is a first-tier diagnostic test for many suspected Mendelian disorders. While it is routine to detect small sequence variants, it is not a standard practice in clinical settings to detect...

    Authors: Ramakrishnan Rajagopalan, Jill R. Murrell, Minjie Luo and Laura K. Conlin

    Citation: Genome Medicine 2020 12:14

    Content type: Research

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  18. For the majority of rare clinical missense variants, pathogenicity status cannot currently be classified. Classical homocystinuria, characterized by elevated homocysteine in plasma and urine, is caused by vari...

    Authors: Song Sun, Jochen Weile, Marta Verby, Yingzhou Wu, Yang Wang, Atina G. Cote, Iosifina Fotiadou, Julia Kitaygorodsky, Marc Vidal, Jasper Rine, Pavel Ješina, Viktor Kožich and Frederick P. Roth

    Citation: Genome Medicine 2020 12:13

    Content type: Research

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  19. Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, a...

    Authors: Gargi Dayama, Sambhawa Priya, David E. Niccum, Alexander Khoruts and Ran Blekhman

    Citation: Genome Medicine 2020 12:12

    Content type: Research

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  20. Carbapenem-resistant Enterobacteriaceae are considered by WHO as “critical” priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producing Escherichia coli (CP-Ec

    Authors: Rafael Patiño-Navarrete, Isabelle Rosinski-Chupin, Nicolas Cabanel, Lauraine Gauthier, Julie Takissian, Jean-Yves Madec, Monzer Hamze, Remy A. Bonnin, Thierry Naas and Philippe Glaser

    Citation: Genome Medicine 2020 12:10

    Content type: Research

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  21. Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatm...

    Authors: Kelly L. Wyres, To N. T. Nguyen, Margaret M. C. Lam, Louise M. Judd, Nguyen van Vinh Chau, David A. B. Dance, Margaret Ip, Abhilasha Karkey, Clare L. Ling, Thyl Miliya, Paul N. Newton, Nguyen Phu Huong Lan, Amphone Sengduangphachanh, Paul Turner, Balaji Veeraraghavan, Phat Voong Vinh…

    Citation: Genome Medicine 2020 12:11

    Content type: Research

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  22. Congenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently....

    Authors: Cigdem Sevim Bayrak, Peng Zhang, Martin Tristani-Firouzi, Bruce D. Gelb and Yuval Itan

    Citation: Genome Medicine 2020 12:9

    Content type: Research

    Published on:

  23. The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies in several cancer types. ...

    Authors: Eoghan R. Malone, Marc Oliva, Peter J. B. Sabatini, Tracy L. Stockley and Lillian L. Siu

    Citation: Genome Medicine 2020 12:8

    Content type: Review

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  24. Modern medicine is rapidly moving towards a data-driven paradigm based on comprehensive multimodal health assessments. Integrated analysis of data from different modalities has the potential of uncovering nove...

    Authors: Ilan Shomorony, Elizabeth T. Cirulli, Lei Huang, Lori A. Napier, Robyn R. Heister, Michael Hicks, Isaac V. Cohen, Hung-Chun Yu, Christine Leon Swisher, Natalie M. Schenker-Ahmed, Weizhong Li, Karen E. Nelson, Pamila Brar, Andrew M. Kahn, Timothy D. Spector, C. Thomas Caskey…

    Citation: Genome Medicine 2020 12:7

    Content type: Research

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  25. Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed si...

    Authors: Kara A. Moser, Elliott F. Drábek, Ankit Dwivedi, Emily M. Stucke, Jonathan Crabtree, Antoine Dara, Zalak Shah, Matthew Adams, Tao Li, Priscila T. Rodrigues, Sergey Koren, Adam M. Phillippy, James B. Munro, Amed Ouattara, Benjamin C. Sparklin, Julie C. Dunning Hotopp…

    Citation: Genome Medicine 2020 12:6

    Content type: Research

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  26. Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution model...

    Authors: Bergthor Björnsson, Carl Borrebaeck, Nils Elander, Thomas Gasslander, Danuta R. Gawel, Mika Gustafsson, Rebecka Jörnsten, Eun Jung Lee, Xinxiu Li, Sandra Lilja, David Martínez-Enguita, Andreas Matussek, Per Sandström, Samuel Schäfer, Margaretha Stenmarker, X. F. Sun…

    Citation: Genome Medicine 2019 12:4

    Content type: Comment

    Published on:

  27. The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) clinical variant interpretation guidelines established criteria for different types of evidence. This incl...

    Authors: Sarah E. Brnich, Ahmad N. Abou Tayoun, Fergus J. Couch, Garry R. Cutting, Marc S. Greenblatt, Christopher D. Heinen, Dona M. Kanavy, Xi Luo, Shannon M. McNulty, Lea M. Starita, Sean V. Tavtigian, Matt W. Wright, Steven M. Harrison, Leslie G. Biesecker and Jonathan S. Berg

    Citation: Genome Medicine 2019 12:3

    Content type: Guideline

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  28. Pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) lead to increased risk of breast, ovarian, and other cancers, but most variant-positive individuals in the general population are unaware of their risk, and little...

    Authors: Noura S. Abul-Husn, Emily R. Soper, Jacqueline A. Odgis, Sinead Cullina, Dean Bobo, Arden Moscati, Jessica E. Rodriguez, Ruth J. F. Loos, Judy H. Cho, Gillian M. Belbin, Sabrina A. Suckiel and Eimear E. Kenny

    Citation: Genome Medicine 2019 12:2

    Content type: Research

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  29. Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differe...

    Authors: Daniel L. McCartney, Futao Zhang, Robert F. Hillary, Qian Zhang, Anna J. Stevenson, Rosie M. Walker, Mairead L. Bermingham, Thibaud Boutin, Stewart W. Morris, Archie Campbell, Alison D. Murray, Heather C. Whalley, David J. Porteous, Caroline Hayward, Kathryn L. Evans, Tamir Chandra…

    Citation: Genome Medicine 2019 12:1

    Content type: Research

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  30. The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority of patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, ...

    Authors: Jitske van den Bulk, Els M. E. Verdegaal, Dina Ruano, Marieke E. Ijsselsteijn, Marten Visser, Ruud van der Breggen, Thomas Duhen, Manon van der Ploeg, Natasja L. de Vries, Jan Oosting, Koen C. M. J. Peeters, Andrew D. Weinberg, Arantza Farina-Sarasqueta, Sjoerd H. van der Burg and Noel F. C. C. de Miranda

    Citation: Genome Medicine 2019 11:87

    Content type: Research

    Published on:

  31. Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are characterised by abnormal epigenetic repression and differentiation of bone marrow haematopoietic stem cells (HSCs). Drugs that reverse epi...

    Authors: Anastasiya Kazachenka, George R. Young, Jan Attig, Chrysoula Kordella, Eleftheria Lamprianidou, Emmanuela Zoulia, George Vrachiolias, Menelaos Papoutselis, Elsa Bernard, Elli Papaemmanuil, Ioannis Kotsianidis and George Kassiotis

    Citation: Genome Medicine 2019 11:86

    Content type: Research

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  32. Variants of uncertain significance represent a massive challenge to medical genetics. Multiplexed functional assays, in which the functional effects of thousands of genomic variants are assessed simultaneously...

    Authors: Hannah Gelman, Jennifer N. Dines, Jonathan Berg, Alice H. Berger, Sarah Brnich, Fuki M. Hisama, Richard G. James, Alan F. Rubin, Jay Shendure, Brian Shirts, Douglas M. Fowler and Lea M. Starita

    Citation: Genome Medicine 2019 11:85

    Content type: Opinion

    Published on:

  33. Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatical...

    Authors: Hannah Demond, Zahra Anvar, Bahia Namavar Jahromi, Angela Sparago, Ankit Verma, Maryam Davari, Luciano Calzari, Silvia Russo, Mojgan Akbarzadeh Jahromi, David Monk, Simon Andrews, Andrea Riccio and Gavin Kelsey

    Citation: Genome Medicine 2019 11:84

    Content type: Research

    Published on:

  34. Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnos...

    Authors: Elias L. Salfati, Emily G. Spencer, Sarah E. Topol, Evan D. Muse, Manuel Rueda, Jonathan R. Lucas, Glenn N. Wagner, Steven Campman, Eric J. Topol and Ali Torkamani

    Citation: Genome Medicine 2019 11:83

    Content type: Research

    Published on:

  35. Circadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. The central circadian clock exerts control over myriad aspects of mammalian physiology, including the regul...

    Authors: Filipa Rijo-Ferreira and Joseph S. Takahashi

    Citation: Genome Medicine 2019 11:82

    Content type: Review

    Published on:

  36. Accurate identification of real somatic variants is a primary part of cancer genome studies and precision oncology. However, artifacts introduced in various steps of sequencing obfuscate confidence in variant ...

    Authors: Hyunbin Kim, Andy Jinseok Lee, Jongkeun Lee, Hyonho Chun, Young Seok Ju and Dongwan Hong

    Citation: Genome Medicine 2019 11:81

    Content type: Software

    Published on:

  37. We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD;...

    Authors: Vahid Bahrambeigi, Xiaofei Song, Karen Sperle, Christine R. Beck, Hadia Hijazi, Christopher M. Grochowski, Shen Gu, Pavel Seeman, Karen J. Woodward, Claudia M. B. Carvalho, Grace M. Hobson and James R. Lupski

    Citation: Genome Medicine 2019 11:80

    Content type: Research

    Published on:

  38. Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown.

    Authors: Sjors Middelkamp, Judith M. Vlaar, Jacques Giltay, Jerome Korzelius, Nicolle Besselink, Sander Boymans, Roel Janssen, Lisanne de la Fonteijne, Ellen van Binsbergen, Markus J. van Roosmalen, Ron Hochstenbach, Daniela Giachino, Michael E. Talkowski, Wigard P. Kloosterman and Edwin Cuppen

    Citation: Genome Medicine 2019 11:79

    Content type: Research

    Published on:

  39. Precision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic,...

    Authors: Jake Lever, Martin R. Jones, Arpad M. Danos, Kilannin Krysiak, Melika Bonakdar, Jasleen K. Grewal, Luka Culibrk, Obi L. Griffith, Malachi Griffith and Steven J. M. Jones

    Citation: Genome Medicine 2019 11:78

    Content type: Research

    Published on:

  40. The 2015 American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that “well-established” functio...

    Authors: Dona M. Kanavy, Shannon M. McNulty, Meera K. Jairath, Sarah E. Brnich, Chris Bizon, Bradford C. Powell and Jonathan S. Berg

    Citation: Genome Medicine 2019 11:77

    Content type: Research

    Published on:

  41. Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their ...

    Authors: Arpad M. Danos, Kilannin Krysiak, Erica K. Barnell, Adam C. Coffman, Joshua F. McMichael, Susanna Kiwala, Nicholas C. Spies, Lana M. Sheta, Shahil P. Pema, Lynzey Kujan, Kaitlin A. Clark, Amber Z. Wollam, Shruti Rao, Deborah I. Ritter, Dmitriy Sonkin, Gordana Raca…

    Citation: Genome Medicine 2019 11:76

    Content type: Correspondence

    Published on:

  42. Inherited susceptibility to common, complex diseases may be caused by rare, pathogenic variants (“monogenic”) or by the cumulative effect of numerous common variants (“polygenic”). Comprehensive genome interpr...

    Authors: Julian R. Homburger, Cynthia L. Neben, Gilad Mishne, Alicia Y. Zhou, Sekar Kathiresan and Amit V. Khera

    Citation: Genome Medicine 2019 11:74

    Content type: Research

    Published on:

  43. Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between...

    Authors: Jian Zhang, Xihao Hu, Jin Wang, Avinash Das Sahu, David Cohen, Li Song, Zhangyi Ouyang, Jingyu Fan, Binbin Wang, Jingxin Fu, Shengqing Gu, Moshe Sade-Feldman, Nir Hacohen, Wuju Li, Xiaomin Ying, Bo Li…

    Citation: Genome Medicine 2019 11:73

    Content type: Research

    Published on:

  44. Artificial intelligence (AI) is the development of computer systems that are able to perform tasks that normally require human intelligence. Advances in AI software and hardware, especially deep learning algor...

    Authors: Raquel Dias and Ali Torkamani

    Citation: Genome Medicine 2019 11:70

    Content type: Review

    Published on:

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