Site Menu
Search Close Search
Search Close Search
Page Menu

Publications

Yingleong Rigel Chan
Publication List

Elaine Lim Publications

Total: 15 results

  • Reliable multiplex generation of pooled induced pluripotent stem cells

    Tuesday, September 26, 2023
    Author(s): Molly Smullen,Meagan N Olson,Julia M Reichert,Pepper Dawes,Liam F Murray,Christina E Baer,Qi Wang,Benjamin Readhead,George M Church,Elaine T Lim,Yingleong Chan
    Source: Cell reports methods
    Reprogramming somatic cells into pluripotent stem cells (iPSCs) enables the study of systems in vitro. To increase the throughput of reprogramming, we present induction of pluripotency from pooled cells (iPPC)-an efficient, scalable, and reliable reprogramming procedure. Using our deconvolution algorithm that employs pooled sequencing of single-nucleotide polymorphisms (SNPs), we accurately estimated individual donor proportions of the pooled iPSCs. With iPPC, we concurrently reprogrammed over...

  • Editorial for the Neurogenetics and Neurogenomics special issue

    Thursday, July 20, 2023
    Author(s): Elaine T Lim,Yingleong Chan
    Source: Human genetics
    No abstract

  • Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus 10398A>G

    Tuesday, June 27, 2023
    Author(s): Molly Smullen,Meagan N Olson,Liam F Murray,Madhusoodhanan Suresh,Guang Yan,Pepper Dawes,Nathaniel J Barton,Jivanna N Mason,Yucheng Zhang,Aria A Fernandez-Fontaine,George M Church,Diego Mastroeni,Qi Wang,Elaine T Lim,Yingleong Chan,Benjamin Readhead
    Source: Scientific reports
    Mitochondrial (MT) dysfunction has been associated with several neurodegenerative diseases including Alzheimer's disease (AD). While MT-copy number differences have been implicated in AD, the effect of MT heteroplasmy on AD has not been well characterized. Here, we analyzed over 1800 whole genome sequencing data from four AD cohorts in seven different tissue types to determine the extent of MT heteroplasmy present. While MT heteroplasmy was present throughout the entire MT genome for blood...

  • FACS-Based Sequencing Approach to Evaluate Cell Type to Genotype Associations Using Cerebral Organoids

    Saturday, June 10, 2023
    Author(s): Liam Murray,Meagan N Olson,Nathaniel Barton,Pepper Dawes,Yingleong Chan,Elaine T Lim
    Source: Methods in molecular biology (Clifton, N.J.)
    Recent technological developments have led to widespread applications of large-scale transcriptomics-based sequencing methods to identify genotype-to-cell type associations. Here we describe a fluorescence-activated cell sorting (FACS)-based sequencing method to utilize CRISPR/Cas9 edited mosaic cerebral organoids to identify or validate genotype-to-cell type associations. Our approach is high-throughput and quantitative and uses internal controls to enable comparisons of the results across...

  • oFlowSeq: a quantitative approach to identify protein coding mutations affecting cell type enrichment using mosaic CRISPR-Cas9 edited cerebral organoids

    Monday, March 06, 2023
    Author(s): Pepper Dawes,Liam F Murray,Meagan N Olson,Nathaniel J Barton,Molly Smullen,Madhusoodhanan Suresh,Guang Yan,Yucheng Zhang,Aria Fernandez-Fontaine,Jay English,Mohammed Uddin,ChangHui Pak,George M Church,Yingleong Chan,Elaine T Lim
    Source: Human genetics
    Cerebral organoids are comprised of diverse cell types found in the developing human brain, and can be leveraged in the identification of critical cell types perturbed by genetic risk variants in common, neuropsychiatric disorders. There is great interest in developing high-throughput technologies to associate genetic variants with cell types. Here, we describe a high-throughput, quantitative approach (oFlowSeq) by utilizing CRISPR-Cas9, FACS sorting, and next-generation sequencing. Using...

  • Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder

    Friday, June 10, 2022
    Author(s): Elaine T Lim,Yingleong Chan,Pepper Dawes,Xiaoge Guo,Serkan Erdin,Derek J C Tai,Songlei Liu,Julia M Reichert,Mannix J Burns,Ying Kai Chan,Jessica J Chiang,Katharina Meyer,Xiaochang Zhang,Christopher A Walsh,Bruce A Yankner,Soumya Raychaudhuri,Joel N Hirschhorn,James F Gusella,Michael E Talkowski,George M Church
    Source: Nature communications
    Cerebral organoids can be used to gain insights into cell type specific processes perturbed by genetic variants associated with neuropsychiatric disorders. However, robust and scalable phenotyping of organoids remains challenging. Here, we perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data. We apply Orgo-Seq to 16p11.2 deletions and 15q11-13 duplications, two loci...

  • Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses

    Thursday, February 11, 2021
    Author(s): Ying Kai Chan,Sean K Wang,Colin J Chu,David A Copland,Alexander J Letizia,Helena Costa Verdera,Jessica J Chiang,Meher Sethi,May K Wang,William J Neidermyer,Yingleong Chan,Elaine T Lim,Amanda R Graveline,Melinda Sanchez,Ryan F Boyd,Thomas S Vihtelic,Rolando Gian Carlo O Inciong,Jared M Slain,Priscilla J Alphonse,Yunlu Xue,Lindsey R Robinson-McCarthy,Jenny M Tam,Maha H Jabbar,Bhubanananda Sahu,Janelle F Adeniran,Manish Muhuri,Phillip W L Tai,Jun Xie,Tyler B Krause,Andyna Vernet,Matthew Pezone,Ru Xiao,Tina Liu,Wei Wang,Henry J Kaplan,Guangping Gao,Andrew D Dick,Federico Mingozzi,Maureen A McCall,Constance L Cepko,George M Church
    Source: Science translational medicine
    Nucleic acids are used in many therapeutic modalities, including gene therapy, but their ability to trigger host immune responses in vivo can lead to decreased safety and efficacy. In the case of adeno-associated viral (AAV) vectors, studies have shown that the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition receptor that senses foreign DNA. Here, we engineered AAV vectors to be intrinsically less immunogenic by incorporating short DNA oligonucleotides that...

  • Publisher Correction: Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

    Thursday, July 16, 2020
    Author(s): Elaine T Lim,Mohammed Uddin,Silvia De Rubeis,Yingleong Chan,Anne S Kamumbu,Xiaochang Zhang,Alissa M D'Gama,Sonia N Kim,Robert Sean Hill,Arthur P Goldberg,Christopher Poultney,Nancy J Minshew,Itaru Kushima,Branko Aleksic,Norio Ozaki,Mara Parellada,Celso Arango,Maria J Penzol,Angel Carracedo,Alexander Kolevzon,Christina M Hultman,Lauren A Weiss,Menachem Fromer,Andreas G Chiocchetti,Christine M Freitag,Autism Sequencing Consortium,George M Church,Stephen W Scherer,Joseph D Buxbaum,Christopher A Walsh
    Source: Nature neuroscience
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • An enhanced CRISPR repressor for targeted mammalian gene regulation

    Wednesday, July 18, 2018
    Author(s): Nan Cher Yeo,Alejandro Chavez,Alissa Lance-Byrne,Yingleong Chan,David Menn,Denitsa Milanova,Chih-Chung Kuo,Xiaoge Guo,Sumana Sharma,Angela Tung,Ryan J Cecchi,Marcelle Tuttle,Swechchha Pradhan,Elaine T Lim,Noah Davidsohn,Mo R Ebrahimkhani,James J Collins,Nathan E Lewis,Samira Kiani,George M Church
    Source: Nature methods
    The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB-MeCP2, to nuclease-dead Cas9. We demonstrate the system's superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and...

  • High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR-Cas9 in yeast

    Wednesday, May 23, 2018
    Author(s): Xiaoge Guo,Alejandro Chavez,Angela Tung,Yingleong Chan,Christian Kaas,Yi Yin,Ryan Cecchi,Santiago Lopez Garnier,Eric D Kelsic,Max Schubert,James E DiCarlo,James J Collins,George M Church
    Source: Nature biotechnology
    Construction and characterization of large genetic variant libraries is essential for understanding genome function, but remains challenging. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions, and insertions) with an efficiency of 80-100% in yeast, along with methods for tracking their fitness en masse. We demonstrate the utility of our approach by characterizing the DNA helicase SGS1 with small tiling deletion...

  • Enabling multiplexed testing of pooled donor cells through whole-genome sequencing

    Saturday, April 21, 2018
    Author(s): Yingleong Chan,Ying Kai Chan,Daniel B Goodman,Xiaoge Guo,Alejandro Chavez,Elaine T Lim,George M Church
    Source: Genome medicine
    We describe a method that enables the multiplex screening of a pool of many different donor cell lines. Our method accurately predicts each donor proportion from the pool without requiring the use of unique DNA barcodes as markers of donor identity. Instead, we take advantage of common single nucleotide polymorphisms, whole-genome sequencing, and an algorithm to calculate the proportions from the sequencing data. By testing using simulated and real data, we showed that our method robustly...

  • Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

    Tuesday, July 18, 2017
    Author(s): Elaine T Lim,Mohammed Uddin,Silvia De Rubeis,Yingleong Chan,Anne S Kamumbu,Xiaochang Zhang,Alissa M D'Gama,Sonia N Kim,Robert Sean Hill,Arthur P Goldberg,Christopher Poultney,Nancy J Minshew,Itaru Kushima,Branko Aleksic,Norio Ozaki,Mara Parellada,Celso Arango,Maria J Penzol,Angel Carracedo,Alexander Kolevzon,Christina M Hultman,Lauren A Weiss,Menachem Fromer,Andreas G Chiocchetti,Christine M Freitag,Autism Sequencing Consortium,George M Church,Stephen W Scherer,Joseph D Buxbaum,Christopher A Walsh
    Source: Nature neuroscience
    We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than...

  • An unbiased index to quantify participant's phenotypic contribution to an open-access cohort

    Saturday, April 08, 2017
    Author(s): Yingleong Chan,Michael Tung,Alexander S Garruss,Sarah W Zaranek,Ying Kai Chan,Jeantine E Lunshof,Alexander W Zaranek,Madeleine P Ball,Michael F Chou,Elaine T Lim,George M Church
    Source: Scientific reports
    The Personal Genome Project (PGP) is an effort to enroll many participants to create an open-access repository of genome, health and trait data for research. However, PGP participants are not enrolled for studying any specific traits and participants choose the phenotypes to disclose. To measure the extent and willingness and to encourage and guide participants to contribute phenotypes, we developed an algorithm to score and rank the phenotypes and participants of the PGP. The scoring algorithm...

  • Directional dominance on stature and cognition in diverse human populations

    Thursday, July 02, 2015
    Author(s): Peter K Joshi,Tonu Esko,Hannele Mattsson,Niina Eklund,Ilaria Gandin,Teresa Nutile,Anne U Jackson,Claudia Schurmann,Albert V Smith,Weihua Zhang,Yukinori Okada,Alena Stančáková,Jessica D Faul,Wei Zhao,Traci M Bartz,Maria Pina Concas,Nora Franceschini,Stefan Enroth,Veronique Vitart,Stella Trompet,Xiuqing Guo,Daniel I Chasman,Jeffery R O'Connel,Tanguy Corre,Suraj S Nongmaithem,Yuning Chen,Massimo Mangino,Daniela Ruggiero,Michela Traglia,Aliki-Eleni Farmaki,Tim Kacprowski,Andrew Bjonnes,Ashley van der Spek,Ying Wu,Anil K Giri,Lisa R Yanek,Lihua Wang,Edith Hofer,Cornelius A Rietveld,Olga McLeod,Marilyn C Cornelis,Cristian Pattaro,Niek Verweij,Clemens Baumbach,Abdel Abdellaoui,Helen R Warren,Dragana Vuckovic,Hao Mei,Claude Bouchard,John R B Perry,Stefania Cappellani,Saira S Mirza,Miles C Benton,Ulrich Broeckel,Sarah E Medland,Penelope A Lind,Giovanni Malerba,Alexander Drong,Loic Yengo,Lawrence F Bielak,Degui Zhi,Peter J van der Most,Daniel Shriner,Reedik Mägi,Gibran Hemani,Tugce Karaderi,Zhaoming Wang,Tian Liu,Ilja Demuth,Jing Hua Zhao,Weihua Meng,Lazaros Lataniotis,Sander W van der Laan,Jonathan P Bradfield,Andrew R Wood,Amelie Bonnefond,Tarunveer S Ahluwalia,Leanne M Hall,Erika Salvi,Seyhan Yazar,Lisbeth Carstensen,Hugoline G de Haan,Mark Abney,Uzma Afzal,Matthew A Allison,Najaf Amin,Folkert W Asselbergs,Stephan J L Bakker,R Graham Barr,Sebastian E Baumeister,Daniel J Benjamin,Sven Bergmann,Eric Boerwinkle,Erwin P Bottinger,Archie Campbell,Aravinda Chakravarti,Yingleong Chan,Stephen J Chanock,Constance Chen,Y-D Ida Chen,Francis S Collins,John Connell,Adolfo Correa,L Adrienne Cupples,George Davey Smith,Gail Davies,Marcus Dörr,Georg Ehret,Stephen B Ellis,Bjarke Feenstra,Mary F Feitosa,Ian Ford,Caroline S Fox,Timothy M Frayling,Nele Friedrich,Frank Geller,Generation Scotland,Irina Gillham-Nasenya,Omri Gottesman,Misa Graff,Francine Grodstein,Charles Gu,Chris Haley,Christopher J Hammond,Sarah E Harris,Tamara B Harris,Nicholas D Hastie,Nancy L Heard-Costa,Kauko Heikkilä,Lynne J Hocking,Georg Homuth,Jouke-Jan Hottenga,Jinyan Huang,Jennifer E Huffman,Pirro G Hysi,M Arfan Ikram,Erik Ingelsson,Anni Joensuu,Åsa Johansson,Pekka Jousilahti,J Wouter Jukema,Mika Kähönen,Yoichiro Kamatani,Stavroula Kanoni,Shona M Kerr,Nazir M Khan,Philipp Koellinger,Heikki A Koistinen,Manraj K Kooner,Michiaki Kubo,Johanna Kuusisto,Jari Lahti,Lenore J Launer,Rodney A Lea,Benjamin Lehne,Terho Lehtimäki,David C M Liewald,Lars Lind,Marie Loh,Marja-Liisa Lokki,Stephanie J London,Stephanie J Loomis,Anu Loukola,Yingchang Lu,Thomas Lumley,Annamari Lundqvist,Satu Männistö,Pedro Marques-Vidal,Corrado Masciullo,Angela Matchan,Rasika A Mathias,Koichi Matsuda,James B Meigs,Christa Meisinger,Thomas Meitinger,Cristina Menni,Frank D Mentch,Evelin Mihailov,Lili Milani,May E Montasser,Grant W Montgomery,Alanna Morrison,Richard H Myers,Rajiv Nadukuru,Pau Navarro,Mari Nelis,Markku S Nieminen,Ilja M Nolte,George T O'Connor,Adesola Ogunniyi,Sandosh Padmanabhan,Walter R Palmas,James S Pankow,Inga Patarcic,Francesca Pavani,Patricia A Peyser,Kirsi Pietilainen,Neil Poulter,Inga Prokopenko,Sarju Ralhan,Paul Redmond,Stephen S Rich,Harri Rissanen,Antonietta Robino,Lynda M Rose,Richard Rose,Cinzia Sala,Babatunde Salako,Veikko Salomaa,Antti-Pekka Sarin,Richa Saxena,Helena Schmidt,Laura J Scott,William R Scott,Bengt Sennblad,Sudha Seshadri,Peter Sever,Smeeta Shrestha,Blair H Smith,Jennifer A Smith,Nicole Soranzo,Nona Sotoodehnia,Lorraine Southam,Alice V Stanton,Maria G Stathopoulou,Konstantin Strauch,Rona J Strawbridge,Matthew J Suderman,Nikhil Tandon,Sian-Tsun Tang,Kent D Taylor,Bamidele O Tayo,Anna Maria Töglhofer,Maciej Tomaszewski,Natalia Tšernikova,Jaakko Tuomilehto,Andre G Uitterlinden,Dhananjay Vaidya,Astrid van Hylckama Vlieg,Jessica van Setten,Tuula Vasankari,Sailaja Vedantam,Efthymia Vlachopoulou,Diego Vozzi,Eero Vuoksimaa,Melanie Waldenberger,Erin B Ware,William Wentworth-Shields,John B Whitfield,Sarah Wild,Gonneke Willemsen,Chittaranjan S Yajnik,Jie Yao,Gianluigi Zaza,Xiaofeng Zhu,The BioBank Japan Project,Rany M Salem,Mads Melbye,Hans Bisgaard,Nilesh J Samani,Daniele Cusi,David A Mackey,Richard S Cooper,Philippe Froguel,Gerard Pasterkamp,Struan F A Grant,Hakon Hakonarson,Luigi Ferrucci,Robert A Scott,Andrew D Morris,Colin N A Palmer,George Dedoussis,Panos Deloukas,Lars Bertram,Ulman Lindenberger,Sonja I Berndt,Cecilia M Lindgren,Nicholas J Timpson,Anke Tönjes,Patricia B Munroe,Thorkild I A Sørensen,Charles N Rotimi,Donna K Arnett,Albertine J Oldehinkel,Sharon L R Kardia,Beverley Balkau,Giovanni Gambaro,Andrew P Morris,Johan G Eriksson,Margie J Wright,Nicholas G Martin,Steven C Hunt,John M Starr,Ian J Deary,Lyn R Griffiths,Henning Tiemeier,Nicola Pirastu,Jaakko Kaprio,Nicholas J Wareham,Louis Pérusse,James G Wilson,Giorgia Girotto,Mark J Caulfield,Olli Raitakari,Dorret I Boomsma,Christian Gieger,Pim van der Harst,Andrew A Hicks,Peter Kraft,Juha Sinisalo,Paul Knekt,Magnus Johannesson,Patrik K E Magnusson,Anders Hamsten,Reinhold Schmidt,Ingrid B Borecki,Erkki Vartiainen,Diane M Becker,Dwaipayan Bharadwaj,Karen L Mohlke,Michael Boehnke,Cornelia M van Duijn,Dharambir K Sanghera,Alexander Teumer,Eleftheria Zeggini,Andres Metspalu,Paolo Gasparini,Sheila Ulivi,Carole Ober,Daniela Toniolo,Igor Rudan,David J Porteous,Marina Ciullo,Tim D Spector,Caroline Hayward,Josée Dupuis,Ruth J F Loos,Alan F Wright,Giriraj R Chandak,Peter Vollenweider,Alan Shuldiner,Paul M Ridker,Jerome I Rotter,Naveed Sattar,Ulf Gyllensten,Kari E North,Mario Pirastu,Bruce M Psaty,David R Weir,Markku Laakso,Vilmundur Gudnason,Atsushi Takahashi,John C Chambers,Jaspal S Kooner,David P Strachan,Harry Campbell,Joel N Hirschhorn,Markus Perola,Ozren Polašek,James F Wilson
    Source: Nature
    Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are...

  • Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development

    Tuesday, April 14, 2015
    Author(s): Yingleong Chan,Rany M Salem,Yu-Han H Hsu,George McMahon,Tune H Pers,Sailaja Vedantam,Tonu Esko,Michael H Guo,Elaine T Lim,GIANT Consortium,Lude Franke,George Davey Smith,David P Strachan,Joel N Hirschhorn
    Source: American journal of human genetics
    Human height is a composite measurement, reflecting the sum of leg, spine, and head lengths. Many common variants influence total height, but the effects of these or other variants on the components of height (body proportion) remain largely unknown. We studied sitting height ratio (SHR), the ratio of sitting height to total height, to identify such effects in 3,545 African Americans and 21,590 individuals of European ancestry. We found that SHR is heritable: 26% and 39% of the total variance of...
Total: 15 results

  • Combined aerobic and strength exercise training on biological ageing in Singaporean breast cancer patients: protocol for the Breast Cancer Exercise Intervention (BREXINT) Pilot Study

    Thursday, March 28, 2024
    Author(s): Patrick Henry Sebastian Sitjar,Si Ying Tan,Mabel Wong,Jingmei Li,Rufaihah Binte Abdul Jalil,Huizhen Aw,Elaine Hsuen Lim,Jorming Goh
    Source: GeroScience
    Breast cancer (BC) is the most prominent cancer amongst women, but fortunately, early diagnosis and advances in multimodality treatments have improved patient survivability. Cancer survivors, however, experience increased biological ageing which may accelerate other co-morbidities. Exercise intervention is a promising clinical adjuvant approach to improve BC patients' physiological function, recovery from treatment, and quality of life. However, the effects of combined aerobic and strength...

  • Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia

    Thursday, March 21, 2024
    Author(s): Salome Funes,Jonathan Jung,Del Hayden Gadd,Michelle Mosqueda,Jianjun Zhong,None Shankaracharya,Matthew Unger,Karly Stallworth,Debra Cameron,Melissa S Rotunno,Pepper Dawes,Megan Fowler-Magaw,Pamela J Keagle,Justin A McDonough,Sivakumar Boopathy,Miguel Sena-Esteves,Jeffrey A Nickerson,Cathleen Lutz,William C Skarnes,Elaine T Lim,Dorothy P Schafer,Francesca Massi,John E Landers,Daryl A Bosco
    Source: Nature communications
    Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs...

  • Cost-effectiveness analysis of add-on pertuzumab to trastuzumab biosimilar and chemotherapy as neoadjuvant treatment for human epidermal growth receptor 2-positive early breast cancer patients in Singapore

    Tuesday, January 30, 2024
    Author(s): Elaine Hsuen Lim,Andrew Lim,Jasmeet Singh Khara,John Cheong,Jek Fong,Sivabalan Sivanesan,Matt Griffiths,Emma New,Soo Chin Lee
    Source: Expert review of pharmacoeconomics & outcomes research
    CONCLUSIONS: This model demonstrated that the long-term clinical impact of early pertuzumab use, particularly the avoidance of metastatic disease and thus avoidance of higher costs and mortality rates, make neoadjuvant pertuzumab a cost-effective option in the management of patients with HER2+ breast cancer in Singapore.

  • Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population

    Wednesday, December 06, 2023
    Author(s): Shaoli Sarker,Tamannyat Binte Eshaque,Anjana Soorajkumar,Nasna Nassir,Binte Zehra,Shayla Imam Kanta,Md Atikur Rahaman,Amirul Islam,Shimu Akter,Mohammad Kawsar Ali,Rabeya Akter Mim,K M Furkan Uddin,Mohammod Shah Jahan Chowdhury,Nusrat Shams,Md Abdul Baqui,Elaine T Lim,Hosneara Akter,Marc Woodbury-Smith,Mohammed Uddin
    Source: Scientific reports
    Duchenne muscular dystrophy (DMD) is a severe rare neuromuscular disorder caused by mutations in the X-linked dystrophin gene. Several mutations have been identified, yet the full mutational spectrum, and their phenotypic consequences, will require genotyping across different populations. To this end, we undertook the first detailed genotype and phenotype characterization of DMD in the Bangladeshi population. We investigated the rare mutational and phenotypic spectrum of the DMD gene in 36...

  • Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway

    Tuesday, November 07, 2023
    Author(s): Peh Joo Ho,Alexis Jiaying Khng,Benita Kiat-Tee Tan,Geok Hoon Lim,Su-Ming Tan,Veronique Kiak Mien Tan,Ryan Shea Ying Cong Tan,Elaine Hsuen Lim,Philip Tsau-Choong Iau,Ying Jia Chew,Yi Ying Lim,Mikael Hartman,Ern Yu Tan,Jingmei Li
    Source: Breast cancer research : BCR
    CONCLUSION: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.

  • Reliable multiplex generation of pooled induced pluripotent stem cells

    Tuesday, September 26, 2023
    Author(s): Molly Smullen,Meagan N Olson,Julia M Reichert,Pepper Dawes,Liam F Murray,Christina E Baer,Qi Wang,Benjamin Readhead,George M Church,Elaine T Lim,Yingleong Chan
    Source: Cell reports methods
    Reprogramming somatic cells into pluripotent stem cells (iPSCs) enables the study of systems in vitro. To increase the throughput of reprogramming, we present induction of pluripotency from pooled cells (iPPC)-an efficient, scalable, and reliable reprogramming procedure. Using our deconvolution algorithm that employs pooled sequencing of single-nucleotide polymorphisms (SNPs), we accurately estimated individual donor proportions of the pooled iPSCs. With iPPC, we concurrently reprogrammed over...

  • Author Correction: Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia

    Wednesday, August 30, 2023
    Author(s): Xiaowei Zhu,Bo Zhou,Reenal Pattni,Kelly Gleason,Chunfeng Tan,Agnieszka Kalinowski,Steven Sloan,Anna-Sophie Fiston-Lavier,Jessica Mariani,Dmitri Petrov,Ben A Barres,Laramie Duncan,Alexej Abyzov,Hannes Vogel,Brain Somatic Mosaicism Network,John V Moran,Flora M Vaccarino,Carol A Tamminga,Douglas F Levinson,Alexander E Urban
    Source: Nature neuroscience
    No abstract

  • Author Correction: The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing

    Tuesday, August 29, 2023
    Author(s): Rachel E Rodin,Yanmei Dou,Minseok Kwon,Maxwell A Sherman,Alissa M D'Gama,Ryan N Doan,Lariza M Rento,Kelly M Girskis,Craig L Bohrson,Sonia N Kim,Ajay Nadig,Lovelace J Luquette,Doga C Gulhan,Brain Somatic Mosaicism Network,Peter J Park,Christopher A Walsh
    Source: Nature neuroscience
    No abstract

  • How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates

    Saturday, July 29, 2023
    Author(s): Zi Lin Lim,Peh Joo Ho,Mikael Hartman,Ern Yu Tan,Nur Khaliesah Binte Mohamed Riza,Elaine Hsuen Lim,Phyu Nitar,None Joint Breast Cancer Registry Jbcr,Fuh Yong Wong,Jingmei Li
    Source: Cancers
    The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first...

  • Editorial for the Neurogenetics and Neurogenomics special issue

    Thursday, July 20, 2023
    Author(s): Elaine T Lim,Yingleong Chan
    Source: Human genetics
    No abstract

  • Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia

    Monday, July 03, 2023
    Author(s): Salome Funes,Del Hayden Gadd,Michelle Mosqueda,Jianjun Zhong,Jonathan Jung,None Shankaracharya,Matthew Unger,Debra Cameron,Pepper Dawes,Pamela J Keagle,Justin A McDonough,Sivakumar Boopathy,Miguel Sena-Esteves,Cathleen Lutz,William C Skarnes,Elaine T Lim,Dorothy P Schafer,Francesca Massi,John E Landers,Daryl A Bosco
    Source: bioRxiv : the preprint server for biology
    Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be fully elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs...

  • Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus 10398A>G

    Tuesday, June 27, 2023
    Author(s): Molly Smullen,Meagan N Olson,Liam F Murray,Madhusoodhanan Suresh,Guang Yan,Pepper Dawes,Nathaniel J Barton,Jivanna N Mason,Yucheng Zhang,Aria A Fernandez-Fontaine,George M Church,Diego Mastroeni,Qi Wang,Elaine T Lim,Yingleong Chan,Benjamin Readhead
    Source: Scientific reports
    Mitochondrial (MT) dysfunction has been associated with several neurodegenerative diseases including Alzheimer's disease (AD). While MT-copy number differences have been implicated in AD, the effect of MT heteroplasmy on AD has not been well characterized. Here, we analyzed over 1800 whole genome sequencing data from four AD cohorts in seven different tissue types to determine the extent of MT heteroplasmy present. While MT heteroplasmy was present throughout the entire MT genome for blood...

  • Breast cancer risk stratification using genetic and non-genetic risk assessment tools for 246,142 women in the UK Biobank

    Monday, June 19, 2023
    Author(s): Peh Joo Ho,Elaine H Lim,Mikael Hartman,Fuh Yong Wong,Jingmei Li
    Source: Genetics in medicine : official journal of the American College of Medical Genetics
    CONCLUSION: Risk-based BC screening may require a multipronged approach that includes PRS, predisposition genes, FH, and other recognized risk factors.

  • FACS-Based Sequencing Approach to Evaluate Cell Type to Genotype Associations Using Cerebral Organoids

    Saturday, June 10, 2023
    Author(s): Liam Murray,Meagan N Olson,Nathaniel Barton,Pepper Dawes,Yingleong Chan,Elaine T Lim
    Source: Methods in molecular biology (Clifton, N.J.)
    Recent technological developments have led to widespread applications of large-scale transcriptomics-based sequencing methods to identify genotype-to-cell type associations. Here we describe a fluorescence-activated cell sorting (FACS)-based sequencing method to utilize CRISPR/Cas9 edited mosaic cerebral organoids to identify or validate genotype-to-cell type associations. Our approach is high-throughput and quantitative and uses internal controls to enable comparisons of the results across...

  • Will Absolute Risk Estimation for Time to Next Screen Work for an Asian Mammography Screening Population?

    Saturday, May 13, 2023
    Author(s): Peh Joo Ho,Elaine Hsuen Lim,Nur Khaliesah Binte Mohamed Ri,Mikael Hartman,Fuh Yong Wong,Jingmei Li
    Source: Cancers
    Personalized breast cancer risk profiling has the potential to promote shared decision-making and improve compliance with routine screening. We assessed the Gail model's performance in predicting the short-term (2- and 5-year) and the long-term (10- and 15-year) absolute risks in 28,234 asymptomatic Asian women. Absolute risks were calculated using different relative risk estimates and Breast cancer incidence and mortality rates (White, Asian-American, or the Singapore Asian population). Using...