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International Conference on Acoustics, Speech, and Signal Processing (ICASSP)

作者： Marcelo A. Colominas Sylvain Meignen Universidad Nacional de Entre Ríos (UNER) Faculty of Engineering Institute for Research and Development in Bioengineering and Bioinformatics (IBB) CONICET Argentina Jean Kuntzmann Laboratory University Grenoble Alpes and CNRS France

In this work, we explore the problem of making synchrosqueezing transform adaptive. To deal with multicomponent signals, existing methods use a fixed order N, thus assuming all the modes making up the signal have order N polynomial phases. To go beyond this limitation, we introduce a new criterion based on the concentration of the representation to locally choose the best order for the synchrosqueezing transform. We study the performance of the proposed approach in terms of the error with respect to the ideal time-frequency representation, both on synthetic and real signals.

关键词： Greedy algorithms Time-frequency analysis Transforms Signal processing Acoustics Proposals Speech processing

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Osteogenic activity of bone: Novel approach of polyvinylidene fluoride films, marrow blood supply, and ultrasound stimulation

SPE Polymers

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SPE Polymers 2023年第4期4卷 175-185页

作者： Zuchuat, Jésica Halter, Christian Zalazar, Martín Faculty of Engineering National University of Entre Ríos Entre Ríos Argentina Institute for Research and Development in Bioengineering and Bioinformatics UNER – CONICET Entre Ríos Argentina

Electric fields used in bone stimulation are based on the application of direct current, but some drawbacks exist, such as the need for an external power source. Piezoelectric poly(vinylidene fluoride) (PVDF) has attracted interest for biomedical applications due to its flexibility, low toxicity, and the piezoelectric response to mechanical stimuli. This study aimed to investigate the effects of PVDF films on bone regeneration in rabbit tibias to assess the potential improvement in osteogenesis. An initial exploratory experiment was performed to determine optimal parameters for regulating the marrow blood supply. The second experiment focused on examining the effects of ultrasound stimulation on the implant's osteogenic capacity. The results showed that PVDF films have a notable impact on the extraskeletal bone formation and bone density in a secluded microenvironment with and without microperforations. At 60 days after surgery, tibias with marrow blood supply reached higher bone volumes and density and they were consistent with the cellular activity. Our results suggest that piezoelectric PVDF films have osteogenic characteristics and can be used to enhance new bone formation in a secluded space, thus reinforcing their biocompatibility nature. Additional studies are required to analyze the benefits of ultrasound stimulation. © 2023 The Authors. SPE Polymers published by Wiley Periodicals LLC on behalf of Society of Plastics Engineers.

关键词： bone tissue engineering osteogenesis piezoelectric polyvinylidene fluoride ultrasound

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A Novel Approach Based on Voronoï Cells to Classify Spectrogram Zeros of Multicomponent Signals

A Novel Approach Based on Voronoï Cells to Classify Spectro...

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International Conference on Acoustics, Speech, and Signal Processing (ICASSP)

作者： N. Laurent S. Meignen M. A. Colominas J. M. Miramont F. Auger LJK University of Grenoble-Alpes and CNRS UMR 5224 Grenoble France Faculty of Engineering (UNER) Oro Verde Institute for Research and Development in Bioengineering and Bioinformatics (IBB UNER - CONICET) Entre Rios Argentina Institut de Recherche en Énergie Électrique de Nantes Atlantique (IREENA UR 4642) Nantes Université Saint-Nazaire France

In this paper, we propose a novel approach to classify the spectrogram zeros (SZs) of multicomponent signals based on the analysis of the Voronoï cells associated with these zeros. More precisely, the characterization of the distribution of the spectrogram maxima of a complex white Gaussian noise along the edges of the Voronoï cells associated with SZs enables us to derive an algorithm to classify the different types of zeros present in the spectrogram of a multicomponent signal. Numerical applications on simulated signals confirm the relevance of the proposed classification algorithm, and an illustration on a real signal concludes the paper.

关键词： Time-frequency analysis Gaussian noise Signal processing algorithms Interference Acoustics Classification algorithms Noise measurement

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Mutational analysis in international isolates and drug repurposing against SARS-CoV-2 spike protein: molecular docking and simulation approach

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VirusDisease 2021年第4期32卷 690-702页

作者： Pulakuntla, Swetha Lokhande, Kiran Bharat Padmavathi, Pannuru Pal, Meena Swamy, Kakumani Venkateswara Sadasivam, Jayashree Singh, Shri Abhiav Aramgam, Sree Latha Reddy, Vaddi Damodara Department of Biochemistry REVA University Bangalore 560064 Karnataka India Bioinformatics Research Laboratory Biotechnology and Bioinformatics Institute Dr. D. Y. Patil Vidyapeeth Pune 411033 Maharashtra India DR Biosciences Research & Development Unit Bettahalasur Bangalore 562157 India Department of Molecular Biology National Institute of Cancer Prevention and Research Noida 20130 Uttar Pradesh India MIT School of Bioengineering Science and Research MIT Art Design and Technology University Pune 412202 Maharashtra India Department of ISRM Indian Council of Medical Research New Delhi 110029 India Department of Radiation Oncology Emory University School of Medicine Atlanta 30329 GA United States

The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is spreading, as the causative pathogen of coronavirus disease-19 (COVID-19). It has infected more than 1.65 billion people all over the world since it was discovered and reported 3.43 million deaths by mid of May 2021. SARS-CoV-2 enters the host cell by binding to viral surface glycoprotein (S protein) with human ACE2 (angiotensin-converting enzyme2). Spike protein (contains S1 and S2 sub-domains) molecular interaction with the host cells is considered as a major step in the viral entry and disease initiation and progression and this identifies spike protein as a promising therapeutic target against antiviral drugs. Currently, there are no efficient antiviral drugs for the prevention of COVID-19 infection. In this study, we have analyzed global 8719 spike protein sequences from patients infected with SAR-CoV-2. These SAR-CoV-2 genome sequences were downloaded from the GISAID database. By using an open reading frame (ORF) tool we have identified the spike protein sequence. With these, all spike protein amino acid sequences are subjected to multiple sequence alignment (MSA) with Wuhan strain spike protein sequence as a query sequence, and it shows all SAR-CoV strain spike proteins are 99.8% identical. In the mutational analysis, we found 639 mutations in the spike protein sequence of SARS-CoV-2 and identified/highlighted 20 common mutations L5F, T22I, T29I, H49Y, L54F, V90F, S98F, S221L, S254F, V367F, A520S, T572I, D614G, H655Y, P809S, A879S, D936Y, A1020S, A1078S, and H1101Y. Further, we have analyzed the crystal structure of the 2019-nCoV chimeric receptor-binding complex with ACE2 (PDB ID: 6VW1) as a major target protein. The spike receptor binding protein (RBD) used as target region for our studies with FDA-approved drugs for repurposing, and identified few anti-SARS-CoV2 potential drugs (Silmitasertib, AC-55541, Merimepodib, XL413, AZ3451) based on their docking score and binding mode calcula

关键词： COVID-19 FDA approved drugs Molecular docking and simulation Mutation analysis SARS-CoV-2

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Site-specific quantification of the in vivo UFMylome reveals myosin modification in ALS

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Cell Reports Methods 2025年第5期5卷 101048页

作者： Blazev, Ronnie Zee, Barry M. Peckham, Hayley Ng, Yaan-Kit Lewis, Christopher T.A. Zhang, Chengxin McNamara, James W. Goodman, Craig A. Gregorevic, Paul Ochala, Julien Steyn, Frederik J. Ngo, Shyuan T. Stokes, Matthew P. Parker, Benjamin L. Department of Anatomy and Physiology The University of Melbourne Parkville 3010 VIC Australia Centre for Muscle Research The University of Melbourne Parkville 3010 VIC Australia Cell Signaling Technology Danvers 01923 MA United States Department of Biomedical Sciences University of Copenhagen Copenhagen 1165 Denmark Novo Nordisk A/S Research and Early Development Måløv 2760 Denmark Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor 48104 MI United States Murdoch Children's Research Institute and Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine The Royal Children's Hospital Parkville 3052 VIC Australia Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine The Royal Children's Hospital Melbourne 3052 VIC Australia Novo Nordisk Foundation Center for Stem Cell Medicine Murdoch Children's Research Institute Melbourne 3052 VIC Australia Department of Neurology University of Washington School of Medicine Seattle 98195 WA United States Department of Neurology Royal Brisbane and Women's Hospital Brisbane 4029 QLD Australia School of Biomedical Sciences The University of Queensland Brisbane 4072 QLD Australia Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane 4072 QLD Australia Centre for Clinical Research The University of Queensland Brisbane 4029 QLD Australia

UFMylation is a ubiquitin-like protein modification of Ubiquitin Fold Modifier 1 (UFM1) applied to substrate proteins and regulates several cellular processes such as protein quality control. Here, we describe the development of an antibody-based enrichment approach to immunoprecipitate remnant UFMylated peptides and identification by mass spectrometry. We used this approach to identify >200 UFMylation sites from various mouse tissues, revealing extensive modification in skeletal muscle. In vivo knockdown of the E2 ligase, UFC1, followed by enrichment and analysis of remnant UFMylated peptides quantified concomitant down-regulation and validation of a subset of modification sites, particularly myosin UFMylation. Furthermore, we show that UFMylation is increased in skeletal muscle biopsies from people living with amyotrophic lateral sclerosis (plwALS). Quantification of UFMylation sites in these biopsies with multiplexed isotopic labeling reveal prominent increases in myosin UFMylation. Our data suggest that in vivo UFMylation is more complex than previously thought. © 2025

关键词： CP: cell biology Ubiquitin Fold Modifier 1 ubiquitin-like modification UFM1 UFMylation

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Genetic discovery in vesicoureteral reflux using exome sequencing: A pilot study

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Medical Journal Armed Forces India 2024年

作者： Thergaonkar, R.W. Manchanda, Vijeta Bansal, Gourja Yadav, Arti Singh, Jyotsna Varma, Binuja Dash, Debasis Mukerji, Mitali Bagga, Arvind Hari, Pankaj Consultant (Pediatrics) & Paed Nephrologist Command Hospital (Eastern Command) Kolkata India Senior Project Fellow (IT) TRISUTRA (Translational Research and Innovative Science ThRough Ayurgenomics) CSIR-Institute of Genomics & Integrative Biology -South Campus Mathura Road near to Sukhdev Vihar New Delhi India Market Development Manager Arrays & Bioinformatics Premas Life Sciences Pvt Ltd Premas Life Sciences Pvt Ltd Delhi New Delhi India Project Manager (Data Science & Research) CORE Diagnostics Gurgaon India PhD Scholar Neuropathology Laboratory Neurosciences Centre All India Institute of Medical Sciences New Delhi India Principal Scientist TCS Life Sciences New Delhi India Chief Scientist CSIR-Institute of Genomics & Integrative Biology -South Campus Mathura Road near to Sukhdev Vihar New Delhi India Professor & Head (Bioscience & Bioengineering) IIT Jodhpur Rajasthan India Professor & Head (Pediatrics) All India Institute of Medical Sciences New Delhi India Professor (Pediatrics Nephrology Division) AIIMS Ansari Nagar New Delhi India

Background: Vesicoureteral reflux (VUR) is a genetically heterogenous disorder. We conducted this pilot study to explore the possibility of genetic discovery in patients with VUR using exome sequencing. Methods: Whole exome sequencing was performed on the DNA of ten Indian children (nine boys) with bilateral grade IV/V reflux and bilateral renal hypodysplasia (extreme phenotype) as well as that of a family with 2 affected male siblings with bilateral VUR and chronic kidney disease. For prioritization of single nucleotide variations (SNVs) in the ten children with extreme phenotype, extremely rare and deleterious variations were selected from a list of 778 genes of biological relevance. Hypothesis-free prioritization was performed in the VUR family. Copy-number variations (CNV) were also called and prioritized from whole exome data. Results: Among ten patients with extreme phenotype, rare and novel and deleterious variants related to VUR and renal hypodysplasia were identified in 7/10 patients each. At least one prioritized variant in either genes related to VUR per se or renal hypodysplasia was seen in 8/10 patients. All patients carried different variations. Among the remaining two patients, one carried a pathogenic CNV. In the VUR family, a rare and deleterious variant in SLIT1 gene was identified. Conclusion: Sharp phenotyping in combination with exome sequencing using a combination of approaches including hypothesis-driven and hypothesis-free for prioritization of SNVs and study of CNVs seems to be an optimal method of genetic discovery of VUR. VUR is genetically heterogenous. © 2024

关键词： Copy-number variation Deconvolution Exome Genetics Vesicoureteral reflux

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Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 47卷 102628-102628页

作者： Chen, Chia-Hung Weng, Tzu-Han Chuang, Cheng-Hsun Huang, Kai-Yao Huang, Sih-Cheng Chen, Pin-Rong Huang, Hsiao-Hsuan Huang, Ling-Ya Shen, Pei-Chun Chuang, Po-Ya Huang, Hsiao-Yen Wu, Yi-Syuan Chang, Hao-Chiun Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan Dependent of Medical Education MacKay Memorial Hospital Taipei10449 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Medicine MacKay Medical College New Taipei City25245 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City11260 Taiwan Drug Development and Value Creation Research Center College of Dental Medicine Kaohsiung Medical University School of Dentistry Graduate Institute of Medicine College of Medicine Center for Cancer Research Kaohsiung Medical University Kaohsiung City80708 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City70101 Taiwan Ph.D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide;the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor. © 2022

关键词： Tumors

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A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy

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Journal of Experimental and Clinical Cancer research 2023年第1期42卷 29-29页

作者： Chen, Chia-Hung Weng, Tzu-Han Huang, Hsiao-Hsuan Huang, Ling-Ya Huang, Kai-Yao Chen, Pin-Rong Yeh, Kuang-Yu Huang, Chi-Ting Chien, Yu-Tzu Chuang, Po-Ya Lin, Yu-Ling Tsai, Nu-Man Liu, Shih-Jen Su, Yu-Cheng Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan Department of Dermatology MacKay Memorial Hospital Taipei City 10449 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Medicine MacKay Medical College New Taipei City 25245 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Agricultural Biotechnology Research Center Academia Sinica Taipei 11529 Taiwan Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung City 40201 Taiwan Department of Pathology and Clinical Laboratory Chung Shan Medical University Hospital Taichung City 40201 Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli 350401 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City 11260 Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung City 80708 Taiwan College of Dental Medicine Kaohsiung Medical University School of Dentistry Kaohsiung City 80708 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City 70101 Taiwan Center for Intelligent Drug Systems and Smart Bio-Devices National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan

Background: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. Methods: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells’ membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. Results: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to st

关键词： Costimulatory molecules Immunotherapy LPPC personalized cancer therapy Tumor heterogenicity

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The repertoire of mutational signatures in human cancer (vol 578, pg 94, 2020)

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NATURE 2023年第7948期614卷 E41-E41页

作者： Alexandrov, Ludmil B. Kim, Jaegil Haradhvala, Nicholas J. Huang, Mi Ni Ng, Alvin Wei Tian Wu, Yang Boot, Arnoud Covington, Kyle R. Gordenin, Dmitry A. Bergstrom, Erik N. Islam, S. M. Ashiqul Lopez-Bigas, Nuria Klimczak, Leszek J. McPherson, John R. Morganella, Sandro Sabarinathan, Radhakrishnan Wheeler, David A. Mustonen, Ville Getz, Gad Rozen, Steven G. Stratton, Michael R. Department of Cellular and Molecular Medicine Department of Bioengineering Moores Cancer Center University of California San Diego CA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Cellular and Molecular Medicine and Department of Bioengineering University of California San Diego La Jolla CA USA UC San Diego Moores Cancer Center San Diego CA USA University of California San Diego San Diego CA USA Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Massachusetts General Hospital Boston MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Laboratory for Medical Science Mathematics RIKEN Center for Integrative Medical Sciences Yokohama Japan Computational Biology Program Ontario Institute for Cancer Research Toronto ON Canada Programme in Cancer & Stem Cell Biology Duke-NUS Medical School Singapore Singapore Centre for Computational Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Centre for Computational Biology Duke-NUS Medical School Singapore Singapore SingHealth Duke-NUS Institute of Precision Medicine National Heart Centre Singapore Singapore Singapore Cancer Science Institute of Singapore National University of Singapore Singapore Singapore Institute of Molecular and Cell Biology Singapore Singapore Laboratory of Cancer Epigenome Division of Medical Science National Cancer Centre Singapore Singapore Singapore Duke-NUS Medical School Singapore Singapore Human Genome Sequencing Center Baylor College of Medicine Houston TX USA Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Genome Integrity and Structural Biology Laboratory National Ins

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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