Katharine Lee

University of Bath

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Misha R. Agarwal

Complete Genomics (United States)

Rebecca Yu Zhang

Complete Genomics (United States)

Radoje Drmanac

Complete Genomics (United States)

Snezana Drmanac

Complete Genomics (United States)

Brock A. Peters

Complete Genomics (United States)

Serban Ciotlos

Flow Pharma (United States)

Daniel M. Hayden

Complete Genomics (United States)

Yuxiang Li

Harbin Engineering University

Emily Park

Yale University

Xuhao Luo

Complete Genomics (United States)

Cooperative Institutions

University of California, San Francisco

Complete Genomics (United States)

Johns Hopkins University

Universidad Católica de Santa Fe

Ames Research Center

San Jose State University

Stanford University

Carnegie Mellon University

University of Washington

Johns Hopkins Medicine

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Repositioning CARE USA

V. Kasturi Rangan Katharine Lee

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Feasibility of Mixed Equipage Operations in the Same Airspace

Parimal Kopardekar Nancy Smith Katharine Lee Arwa Aweiss Paul U. Lee

This study used a human-in-the-loop simulation to examine the feasibility of mixed equipage operations in an automated separation assurance environment under higher traffic densities. The study involved two aircraft equipage alternatives - with and without data link- and four traffic conditions. In all traffic conditions the unequipped traffic count was increased linearly throughout the scenario from approximately 5 to 20 aircraft. Condition One consisted solely of this unequipped traffic, while the remaining three conditions also included a constant number of equipped aircraft operating within the same airspace: 15 equipped aircraft in condition two, 30 in condition three, and 45 in condition four. If traffic load became excessive during any run, participants were instructed to refuse sector entry to inbound unequipped aircraft until sector load became manageable. Results showed a progressively higher number of unequipped aircraft turned away under the second, third, and fourth scenario conditions. Controller workload also increased progressively. Participants rated the mixed operations concept as acceptable, with some qualifications about procedures and information displays. These results showed that mixed operations might be feasible in the same airspace, if unequipped aircraft count is held to a workable level. This level will decrease with increasing complexity. The results imply that integrated airspace configuration is feasible to a limit. The results also indicate that the conflict detection and resolution automation, equipage, and traffic density are important factors that will need to be considered for airspace configuration.

Separation (statistics)

Air traffic controller

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Sustainability at Millipore

Michael W. Toffel Katharine Lee

This case describes Millipore Corporation's approach to becoming a more environmentally sustainable company. As he prepared for his quarterly meeting with the CEO, the Director of Sustainability needed to develop positions on several issues. Tactically, he needed to recommend whether the company should purchase carbon offsets to help meet its aggressive greenhouse gas reduction targets, and whether to continue publicly reporting its greenhouse gas emissions and strategies despite recent problems. On a more strategic level, he needed to recommend how to take the company's Sustainability Initiative to the next level, and consider whether changes were needed to its organizational structure. Finally, he needed to develop a more systematic approach to prioritizing investments in various projects being proposed to improve environmental performance. The case provides a background of the sustainability movement, and reviews major sustainability frameworks (including The Natural Step, Carbon Footprints, and the Sustainability Hierarchy) and prevailing sustainability performance metrics.

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Carbon Footprint

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Data from Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

Natali Gulbahce Mark Jesus M. Magbanua Robert Chin Misha R. Agarwal Xuhao Luo

<div>AbstractMuch effort has been dedicated to developing circulating tumor cells (CTC) as a noninvasive cancer biopsy, but with limited success as yet. In this study, we combine a method for isolation of highly pure CTCs using immunomagnetic enrichment/fluorescence-activated cell sorting with advanced whole genome sequencing (WGS), based on long fragment read technology, to illustrate the utility of an accurate, comprehensive, phased, and quantitative genomic analysis platform for CTCs. Whole genomes of 34 CTCs from a patient with metastatic breast cancer were analyzed as 3,072 barcoded subgenomic compartments of long DNA. WGS resulted in a read coverage of 23× per cell and an ensemble call rate of >95%. These barcoded reads enabled accurate detection of somatic mutations present in as few as 12% of CTCs. We found in CTCs a total of 2,766 somatic single-nucleotide variants and 543 indels and multi-base substitutions, 23 of which altered amino acid sequences. Another 16,961 somatic single nucleotide variant and 8,408 indels and multi-base substitutions, 77 of which were nonsynonymous, were detected with varying degrees of prevalence across the 34 CTCs. On the basis of our whole genome data of mutations found in all CTCs, we identified driver mutations and the tissue of origin of these cells, suggesting personalized combination therapies beyond the scope of most gene panels. Taken together, our results show how advanced WGS of CTCs can lead to high-resolution analyses of cancers that can reliably guide personalized therapy. Cancer Res; 77(16); 4530–41. ©2017 AACR.</div>

Indel

Circulating tumor cell

Liquid biopsy

Personalized Medicine

10.1158/0008-5472.c.6508917

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Figure S2 from Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

Natali Gulbahce Mark Jesus M. Magbanua Robert Chin Misha R. Agarwal Xuhao Luo

Prevalence difference between early and late collection time points. We used allele fraction (prevalence), the ratio of compartments with reads supporting variant calls versus total calls, to further analyze changes between two collection time points, Early and Late. For each variant, prevalence was calculated using cells collected at Early and Late separately. Distribution of the difference between Early and Late prevalence are plotted. The prevalence difference between the two time points indicates whether tumor lineages stayed the same (difference = 0) or increased or decreased. The peak of the distribution is at 0 indicating tumor lineages survived the treatment, which is consistent with a lack of tumor response between these time points.

10.1158/0008-5472.22414218.v1

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Figure S4 from Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

Natali Gulbahce Mark Jesus M. Magbanua Robert Chin Misha R. Agarwal Xuhao Luo

Copy number analysis based on read coverage in all batches. Read data is plotted starting from Chr1 and ending at ChrX. Each sample is labeled on the right side of the plot. All CTC samples identify chr1q amplification, and chr13 and chr16q losses.

Cancer Therapy

Sample (material)

10.1158/0008-5472.22414212.v1

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Supplementary Tables from Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

Natali Gulbahce Mark Jesus M. Magbanua Robert Chin Misha R. Agarwal Xuhao Luo

The following file contains Tables S1-12. The contents of these tables are referenced through the manuscript and contain the basis for the results summarized in the paper. The list of tables is as follows: S1. CNV. This table contains all the copy number gains and losses identified in the CTCs. S2. SNV. This table contains all of the somatic SNVs identified in the CTCs. S3. Indel. This table contains all of the somatic insertions and deletions identified in the CTCs. S4. NA12877 somatic. This table contains all of the somatic SNVs identified in NA12877. S5. Allele fraction. This table contains allele fraction calculations and compartment number filtering calculations. S6. Sanger and Miseq. This table contains all of the Sanger sequencing and Miseq validation for the 77 somatic SNVs validated in this study. S7. Mutational spectrum. This table contains the mutation spectrum analysis and the comparison of the CTC mutation spectrum to other tumor types. S8. Non-coding annotation. This table contains a list of potentially important somatic noncoding variants. S9. Splicing. This table contains somatic splicing variants. S10. MHC-II. This table contains the potential somatic coding changes which would result in MHC-II binding antigens. S11. Two hit. This table contains genes with two potential inactivating variants, this can include inherited and somatic variants. S12. Phasing. This table contains phased somatic and/or inherited variants that potentially inactivate a gene through a compound heterozygous mechanism.

Sanger sequencing

10.1158/0008-5472.22414206

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Figure S3 from Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

Natali Gulbahce Mark Jesus M. Magbanua Robert Chin Misha R. Agarwal Xuhao Luo

Mutational spectrum of CTCs. The percent of particular base changes (labeled on the right of the figure) for different sets of mutations from CTCs, NA12877, and breast cancer from TCGA (BRCA) data are shown. Founder mutations and mutations found in 5 cells have a pattern very similar to that seen in breast cancer.

Circulating tumor cell

10.1158/0008-5472.22414215.v1

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Gilead Sciences, Inc.: Access Program

V. Kasturi Rangan Katharine Lee

Gilead Sciences, the U.S. leader in HIV/AIDS medicines, with global sales of $5.4 billion in 2009, had undertaken several innovative actions to make its anti-viral products available to over 100 low- and middle-income countries. Having reached nearly 680,000 patients by the middle of 2009, the company's senior managers contemplated how to reach 2 million patients by 2012.

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Physical Activity Analysis: A project in many languages

Katharine Lee

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