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Supplementary Figure A6-2 from High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Supplementary Figure A6-1 from High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Supplementary Table 1 from High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Gene expression analysis has identified biologically relevant subclasses of breast cancer. However, most classification schemes do not robustly cluster all HER2+ breast cancers, in part due to limitations and bias of clustering techniques used. In this article, we propose an alternative approach that first separates the HER2+ tumors using a gene amplification signal for Her2/neu amplicon genes and then applies consensus ensemble clustering separately to the HER2+ and HER2− clusters to look for further substructure. We applied this procedure to a microarray data set of 286 early-stage breast cancers treated only with surgery and radiation and identified two basal and four luminal subtypes in the HER2− tumors, as well as two novel and robust HER2+ subtypes. HER2+ subtypes had median distant metastasis-free survival of 99 months [95% confidence interval (95% CI), 83–118 months] and 33 months (95% CI, 11–54 months), respectively, and recurrence rates of 11% and 58%, respectively. The low recurrence subtype had a strong relative overexpression of lymphocyte-associated genes and was also associated with a prominent lymphocytic infiltration on histologic analysis. These data suggest that early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history. [Cancer Res 2007;67(22):10669–76]

Supplementary Table 3a from High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Supplementary Appendix 1 from High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Supplementary Table 2 from High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Naturally occurring microbial communities often comprise thousands of taxa involved in complex networks of interactions. These interactions can be mediated by several mechanisms, including the competition for resources, the exchange of signals and nutrients, cell-cell contact and antibiotic warfare. In addition to direct measurements and computational predictions of interactions, abundant data on microbial co-occurrence associations can be inferred from correlations of taxa across samples, which can be estimated from metagenomic, and amplicon datasets. The analysis and interpretation of interaction and correlation networks are limited by the challenge of comparing across different datasets, due to heterogeneity of the data itself and to the lack of a platform to facilitate such comparisons. Here, we introduce the Microbial Interaction Network Database (MIND) - a web-based platform for the integrative analysis of different types of microbial networks, freely available at http://microbialnet.org/. In addition to containing a growing body of curated data, including amplicon-based co-occurrence networks, genome-scale model-derived networks, metabolic influence networks and horizontal gene transfer networks, MIND allows users to upload and analyze newly generated networks using a JSON format and standard NCBI taxonomy. The platform provides convenient functions to compare and query multiple networks simultaneously, and to visualize and export networks and datasets. Through some illustrative examples, we demonstrate how the platform might facilitate discoveries and help generate new hypotheses on host-associated and environmentally important microbial ecosystems through the power of knowledge integration.

Background: As the SARS-Cov-2/Covid-19 pandemic continues to ravage the world, it is important to understanding the characteristics of its spread and possible correlates for control to develop strategies of response. Methods: Here we show how a simple Susceptible-Infective-Recovered (SIR) model applied to data for eight European countries and the United Kingdom (UK) can be used to forecast the descending limb (post-peak) of confirmed cases and deaths as a function of time, and predict the duration of the pandemic once it has peaked, by estimating and fixing parameters using only characteristics of the ascending limb and the magnitude of the first peak. Results: The predicted and actual case fatality ratio, or number of deaths per million population from the start of the pandemic to when daily deaths number less than five for the first time, was lowest in Norway (predicted: 44 5 deaths/million; actual: 36 deaths/million) and highest for the United Kingdom (predicted: 578 +/- 65 deaths/million; actual 621 deaths/million). The inferred pandemic characteristics separated into two distinct groups: those that are largely invariant across countries, and those that are highly variable. Among the former is the infective period, TL = 16.3 2.7 days, the average time between contacts, TR = 3.8+/- 0.5 days and the average number of contacts while infective R = 4.4 +/- 0.5. In contrast, there is a highly variable time lag TD between the peak in the daily number of confirmed cases and the peak in the daily number of deaths, ranging from lows of TD = 2,4 days for Denmark and Italy respectively, to highs of TD = 12, 15 for Germany and Norway respectively. The mortality fraction, or ratio of deaths to confirmed cases, was also highly variable, ranging from low values 3%, 5% and 5% for Norway, Denmark and Germany respectively, to high values of 18%, 20% and 21% for Sweden, France, and the UK respectively. The probability of mortality rather than recovery was a significant correlate of the duration of the pandemic, defined as the time from 12/31/2019 to when the number of daily deaths fell below 5. Finally, we observed a small but detectable effect of average temperature on the probability of infection per contact, with higher temperatures associated with lower infectivity. Conclusions: Our simple model captures the dynamics of the initial stages of the pandemic, from its exponential beginning to the first peak and beyond, with remarkable precision. As with all epidemiological analyses, unanticipated behavioral changes will result in deviations between projection and observation. This is abundantly clear for the current pandemic. Nonetheless, accurate short-term projections are possible, and the methodology we present is a useful addition to the epidemiologist's armamentarium. Our predictions assume that control measures such as lockdown, social distancing, use of masks etc. remain the same post-peak as before peak. Consequently, deviations from our predictions are a measure of the extent to which loosening of control measures have impacted case-loads and deaths since the first peak and initial decline in daily cases and deaths. Our findings suggest that the two key parameters to control and reduce the impact of a developing pandemic are the infective period and the mortality fraction, which are achievable by early case identification, contact tracing and quarantine (which would reduce the former) and improving quality of care for identified cases (which would reduce the latter).

Microbes tend to organize into communities consisting of hundreds of species involved in complex interactions with each other. 16S ribosomal RNA (16S rRNA) amplicon profiling provides snapshots that reveal the phylogenies and abundance profiles of these microbial communities. These snapshots, when collected from multiple samples, have the potential to reveal which microbes co-occur, providing a glimpse into the network of associations in these communities. The inference of networks from 16S data is prone to statistical artifacts. There are many tools for performing each step of the 16S analysis workflow, but the extent to which these steps affect the final network is still unclear. In this study, we perform a meticulous analysis of each step of a pipeline that can convert 16S sequencing data into a network of microbial associations. Through this process, we map how different choices of algorithms and parameters affect the co-occurrence network and estimate steps that contribute most significantly to the variance. We further determine the tools and parameters that generate the most accurate and robust co-occurrence networks based on comparison with mock and synthetic datasets. Ultimately, we develop a standardized pipeline (available at https://github.com/segrelab/MiCoNE) that follows these default tools and parameters, but that can also help explore the outcome of any other combination of choices. We envisage that this pipeline could be used for integrating multiple data-sets, and for generating comparative analyses and consensus networks that can help understand and control microbial community assembly in different biomes.ImportanceTo understand and control the mechanisms that determine the structure and function of microbial communities, it is important to map the interrelationships between its constituent microbial species. The surge in the high-throughput sequencing of microbial communities has led to the creation of thousands of datasets containing information about microbial abundances. These abundances can be transformed into networks of co-occurrences across multiple samples, providing a glimpse into the structure of microbiomes. However, processing these datasets to obtain co-occurrence information relies on several complex steps, each of which involves multiple choices of tools and corresponding parameters. These multiple options pose questions about the accuracy and uniqueness of the inferred networks. In this study, we address this workflow and provide a systematic analysis of how these choices of tools and parameters affect the final network, and on how to select those that are most appropriate for a particular dataset.

Understanding the characteristics of the SARS-Cov-2/Covid-19 pandemic is central to developing control strategies. Here we show how a simple Susceptible-Infective-Recovered (SIR) model applied to data for eight European countries and the United Kingdom (UK) can be used to forecast the descending limb (post-peak) of confirmed cases and deaths as a function of time, and predict the duration of the pandemic once it has peaked, by estimating and fixing parameters using only characteristics of the ascending limb and the magnitude of the first peak. As with all epidemiological analyses, unanticipated behavioral changes will result in deviations between projection and observation. This is abundantly clear for the current pandemic. Nonetheless, accurate short-term projections are possible, and the methodology we present is a useful addition to the epidemiologist’s armamentarium. Since our predictions assume that control measures such as lockdown, social distancing, use of masks etc. remain the same post-peak as before peak, deviations from our predictions are a measure of the extent to which loosening of control measures have impacted case-loads and deaths since the first peak and initial decline in daily cases and deaths. The predicted and actual case fatality ratio, or number of deaths per million population from the start of the pandemic to when daily deaths number less than five for the first time, was lowest in Norway (pred: 44 ± 5 deaths/million; actual: 36 deaths/million) and highest for the United Kingdom (pred: 578 +/- 65 deaths/million; actual 621 deaths/million). The inferred pandemic characteristics separated into two distinct groups: those that are largely invariant across countries, and those that are highly variable. Among the former is the infective period, ; the average time between contacts, and the average number of contacts while infective, . In contrast, there is a highly variable time lag TD between the peak in the daily number of confirmed cases and the peak in the daily number of deaths, ranging from a low of TD = 2,4 days for Denmark and Italy respectively, to highs of TD = 12, 15 for Germany and Norway respectively. The mortality fraction, or ratio of deaths to confirmed cases, was also highly variable, ranging from low values 3%, 5% and 5% for Norway, Denmark and Germany respectively, to high values of 18%, 20% and 21% for Sweden, France, and the UK respectively. The probability of mortality rather than recovery was a significant correlate of the duration of the pandemic, defined as the time from 12/31/2019 to when the number of daily deaths fell below 5. Finally, we observed a small but detectable effect of average temperature on the probability α of infection per contact, with higher temperatures associated with lower infectivity. Policy implications of our findings are also briefly discussed.

The long atmospheric residence time of CO 2 creates an urgent need to add atmospheric carbon drawdown to CO 2 regulatory strategies. Synthetic and systems biology (SSB), which enables manipulation of cellular phenotypes, offers a powerful approach to amplifying and adding new possibilities to current land management practices aimed at reducing atmospheric carbon. The participants (in attendance: Christina Agapakis, George Annas, Adam Arkin, George Church, Robert Cook-Deegan, Charles DeLisi, Dan Drell, Sheldon Glashow, Steve Hamburg, Henry Jacoby, Henry Kelly, Mark Kon, Todd Kuiken, Mary Lidstrom, Mike MacCracken, June Medford, Jerry Melillo, Ron Milo, Pilar Ossorio, Ari Patrinos, Keith Paustian, Kristala Jones Prather, Kent Redford, David Resnik, John Reilly, Richard J. Roberts, Daniel Segre, Susan Solomon, Elizabeth Strychalski, Chris Voigt, Dominic Woolf, Stan Wullschleger, and Xiaohan Yang) identified a range of possibilities by which SSB might help reduce greenhouse gas concentrations and which might also contribute to environmental sustainability and adaptation. These include, among other possibilities, engineering plants to convert CO 2 produced by respiration into a stable carbonate, designing plants with an increased root-to-shoot ratio, and creating plants with the ability to self-fertilize. A number of serious ecological and societal challenges must, however, be confronted and resolved before any such application can be fully assessed, realized, and deployed.