Recent genome-wide CRISPR-Cas9 loss-of-function screens have identified genetic dependencies across many cancer cell lines. Associations between these dependencies and genomic alterations in the same ...cell lines reveal phenomena such as oncogene addiction and synthetic lethality. However, comprehensive identification of such associations is complicated by complex interactions between genes across genetically heterogeneous cancer types. We introduce and apply the algorithm SuperDendrix to CRISPR-Cas9 loss-of-function screens from 769 cancer cell lines, to identify differential dependencies across cell lines and to find associations between differential dependencies and combinations of genomic alterations and cell-type-specific markers. These associations respect the position and type of interactions within pathways: for example, we observe increased dependencies on downstream activators of pathways, such as NFE2L2, and decreased dependencies on upstream activators of pathways, such as CDK6. SuperDendrix also reveals dozens of dependencies on lineage-specific transcription factors, identifies cancer-type-specific correlations between dependencies, and enables annotation of individual mutated residues.
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SuperDendrix finds associations between sample features and CRISPR genetic dependenciesSomatic mutations are associated with 127 genetic dependencies from Project DepMapLineage-specific dependencies on transcription factors correlate with gene expressionIdentified associations agree with direction of interactions within oncogenic pathways
Using SuperDendrix, Park et al. examine associations between genetic dependencies in 769 cancer cell lines. They report 127 genetic dependencies explained by combinations of mutually exclusive somatic mutations congregating into a few oncogenic pathways across cancer subtypes. These present a small number of prominent and highly specific genetic vulnerabilities in cancer.
Discussions of rural development policy are for the most part focused on the tenurial, institutional, technical, infrastructural, and economic aspects of agricultural development. In contrast, ...nonfarm activities in agricultural regions receive little attention, and a number of models of agrarian economies with nonfarm activities have even predicted a decline of such activities with agricultural development. It is shown here that nonfarm activities in agricultural regions expand quite rapidly in response to agricultural development and merit special attention in the design of rural and urban development strategies.The extent and importance of nonfarm activities in rural areas and towns is examined from the viewpoint of their contribution to the output, employment, and earnings of the rural labor force. Nonfarm activities become increasingly concentrated in rural towns in response to infrastructure improvements and the growth of markets. Besides being of benefit to the activities themselves, the process appears to stimulate a degree of decentralization of urban growth, providing added employment and earnings opportunities fr the out-migrants from agriculture as agricultural productivity rises. Nonfarm activities in rural areas and towns are thus an essential element in the process of economic development and structural change from rural-agricultural to urban-industrial economies. Appendices.
The Indonesian labour force is expected to grow by over 1 million workers in each of the next few years, about half of this increment taking place in the already densely populated island of Java ...where agricultural employment is approaching saturation point. This acceleration of labour force growth and the quickening pace of industrialisation threaten to upset the precarious rural-urban balance of recent years and pose complex problems of employment policy. The author believes that despite their limitations current government programmes, particularly the local public works scheme, provide a good foundation on which further official efforts to generate employment might be developed. He advocates a gradual approach carefully integrating programme objectives with the specific employment components and the broader goals of balanced rural and urban development, satisfactory rates of growth, modernisation, etc. Due attention should be given, inter alia, to suitable vocational preparation and the reform of labour market institutions
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