Dual gene activation and knockout screen reveals directional dependencies in genetic networks.

Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct a directional dependency network for human K562 leukemia cells and demonstrate how our approach allows the determination of directionality in activating genetic interactions. Our interaction network connects previously uncharacterized genes to well-studied pathways and identifies targets relevant for therapeutic intervention

Homogeneous Plane-wave Spacetimes and their Stability

We consider the stability of spatially homogeneous plane-wave spacetimes. We carry out a full analysis for plane-wave spacetimes in (4+1) dimensions, and find there are two cases to consider; what we call non-exceptional and exceptional. In the non-exceptional case the plane waves are stable to (spatially homogeneous) vacuum perturbations as well as a restricted set of matter perturbations. In the exceptional case we always find an instability. Also we consider the Milne universe in arbitrary dimensions and find it is also stable provided the strong energy condition is satisfied. This implies that there exists an open set of stable plane-wave solutions in arbitrary dimensions.Comment: 15 pages, no figures; minor changes, new references, to appear in CQ

On Horizons and Plane Waves

We investigate the possibility of having an event horizon within several classes of metrics that asymptote to the maximally supersymmetric IIB plane wave. We show that the presence of a null Killing vector (not necessarily covariantly constant) implies an effective separation of the Einstein equations into a standard and a wave component. This feature may be used to generate new supergravity solutions asymptotic to the maximally supersymmetric IIB plane wave, starting from standard seed solutions such as branes or intersecting branes in flat space. We find that in many cases it is possible to preserve the extremal horizon of the seed solution. On the other hand, non-extremal deformations of the plane wave solution result in naked singularities. More generally, we prove a no-go theorem against the existence of horizons for backgrounds with a null Killing vector and which contain at most null matter fields. Further attempts at turning on a nonzero Hawking temperature by introducing additional matter have proven unsuccessful. This suggests that one must remove the null Killing vector in order to obtain a horizon. We provide a perturbative argument indicating that this is in fact possible.Comment: 46 pp, 1 figur

The Problem of Experience in the Study of Organizations

This paper deals with the fact that we cannot experience large organizations directly, in the same way as we can experience individuals or small groups, and that this non-experientiability has certain implications for our scientific theories of organizations. Whereas a science is animated by a constructive interplay of theory concepts and experience concepts, the study of organizations has been confined to theory concepts alone. Implications of this analysis for developing a science of organizations are considered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68303/2/10.1177_017084069301400102.pd

KG-COVID-19: A Framework to Produce Customized Knowledge Graphs for COVID-19 Response.

Integrated, up-to-date data about SARS-CoV-2 and COVID-19 is crucial for the ongoing response to the COVID-19 pandemic by the biomedical research community. While rich biological knowledge exists for SARS-CoV-2 and related viruses (SARS-CoV, MERS-CoV), integrating this knowledge is difficult and time-consuming, since much of it is in siloed databases or in textual format. Furthermore, the data required by the research community vary drastically for different tasks; the optimal data for a machine learning task, for example, is much different from the data used to populate a browsable user interface for clinicians. To address these challenges, we created KG-COVID-19, a flexible framework that ingests and integrates heterogeneous biomedical data to produce knowledge graphs (KGs), and applied it to create a KG for COVID-19 response. This KG framework also can be applied to other problems in which siloed biomedical data must be quickly integrated for different research applications, including future pandemics

Group Process and Organizational Environment: Student Organizations in the University

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68768/2/10.1177_089976407400300305.pd

The Human Phenotype Ontology in 2024: phenotypes around the world

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

A Chemistry of Organization: Combinatory Structural Analysis and Design

This paper is a response to the call for models of organization design as a science revealing the inner composition of organization and specifying the laws to be respected when crafting it. It maintains that the needed science is a chemistry of organization, addressing the combination of 'organizational elements' playing a role analogous to that of chemical elements in composing a variety of substances. Drawing both on classic organization design theory and on configurational and complementarity-based approaches, the paper specifies a set of basic organizational elements and a set of combinatory laws regulating their effective combinations. Testable propositions are derived on the necessary and sufficient conditions that the composition of organizations should have respect for achieving high levels of efficiency and innovation. These propositions are tested empirically on a sample of firms, using an innovative application of Boolean algebra

The Ups and Downs in Women's Employment: Shifting Composition or Behavior from 1970 to 2010?

This paper tracks factors contributing to the ups and downs in women’s employment from 1970 to 2010 using regression decompositions focusing on whether changes are due to shifts in the means (composition of women) or due to shifts in coefficients (inclinations of women to work for pay). Compositional shifts in education exerted a positive effect on women’s employment across all decades, while shifts in the composition of other family income, particularly at the highest deciles, depressed married women’s employment over the 1990s contributing to the slowdown in this decade. A positive coefficient effect of education was found in all decades, except the 1990s, when the effect was negative, depressing women’s employment. Further, positive coefficient results for other family income at the highest deciles bolstered married women’s employment over the 1990s. Models are run separately for married and single women demonstrating the varying results of other family income by marital status. This research was supported in part by an Upjohn Institute Early Career Research Award