Machine learning could improve innovation policy

Accepted manuscrip

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

When Collaboration Bridges Institutions: The Impact of University–Industry Collaboration on Academic Productivity

Prior research suggests that academic scientists who collaborate with firms may experience lower publication rates in their collaborative lines of work due to industry’s insistence on intellectual property protection through patenting or secrecy. In contrast, we posit that university–industry collaboration can sometimes foster specialization and boost academic contribution to open science. Specifically, research lines with both scientific and commercial potential (i.e., in Pasteur’s quadrant) provide an opportunity for a productive division of tasks between academic scientists and their industry counterparts, whereby the former focus on exploiting the scientific opportunities and the latter focus on the commercial ones. The main empirical challenge of examining this proposition is that research projects that involve industry collaborators may be qualitatively different from those that do not. To address this issue, we exploit the occurrence of simultaneous discoveries where multiple scientists make roughly the same discovery around the same time. Following a simultaneous discovery, we compare the follow-on research output of academic scientists who collaborated with industry on the discovery with that of academic scientists who did not. We find that academic scientists with industry collaborators produced more follow-on publications and fewer follow-on patents than did academic scientists without industry collaborators. This effect is particularly salient when the research line has important commercial implications and when the industry partner is an established firm

Automation, research technology, and researchers’ trajectories: evidence from computer science and electrical engineering

We examine how the introduction of a technology that automates research tasks influences the rate and type of researchers’ knowledge production. To do this, we leverage the unanticipated arrival of an automating motion-sensing research technology that occurred as a consequence of the introduction and subsequent hacking of the Microsoft Kinect system. To estimate whether this technology induces changes in the type of knowledge produced, we employ novel measures based on machine learning (topic modeling) techniques and traditional measures based on bibliometric indicators. Our analysis demonstrates that the shock associated with the introduction of Kinect increased the production of ideas and induced researchers to pursue ideas more diverse than and distant from their original trajectories. We find that this holds for both researchers who had published in motion-sensing research prior to the Kinect shock (within-area researchers) and those who did not (outside-area researchers), with the effects being stronger among outside-area researchers.Published versio

Detrimental Collaborations in Creative Work: Evidence from Economics

Prior research on collaboration and creativity often assumes that individuals choose to collaborate to improve the quality of their output. Given the growing role of collaboration and autonomous teams in creative work, the validity of this assumption has important implications for organizations. We argue that in the presence of a collaboration credit premium—when the sum of fractional credit allocated to each collaborator exceeds 100%— individuals may choose to work together even when the project output is of low quality or when its prospects are diminished by collaborating. We test our argument on a sample of economists in academia using the norm of alphabetical ordering of authors’ surnames on academic articles as an instrument for selection into collaboration. This norm means that economists whose family name begins with a letter from the beginning of the alphabet receive systematically more credit for collaborative work than economists whose family name begins with a letter from the end of the alphabet. We show that, in the presence of a credit premium, individuals may choose to collaborate even if this choice decreases output quality. Thus, collaboration can create a misalignment between the incentives of creative workers and the prospects of the project

Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines

Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription–quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes

Creativity at the Knowledge Frontier: The Impact of Specialization in Fast- and Slow-paced Domains

Using the impact of the Soviet Union’s collapse on the performance of theoretical mathematicians as a natural experiment, we attempt to resolve the controversy in prior research on whether specialists or generalists have superior creative performance. While many have highlighted generalists’ advantage due to access to a wider set of knowledge components, others have underlined the benefits that specialists can derive from their deep expertise. We argue that this disagreement might be partly driven by the fact that the pace of change in a knowledge domain shapes the relative return from being a specialist or a generalist. We show that generalist scientists performed best when the pace of change was slower and their ability to draw from diverse knowledge domains was an advantage in the field, but specialists gained advantage when the pace of change increased and their deeper expertise allowed them to use new knowledge created at the knowledge frontier. We discuss and test the roles of cognitive mechanisms and of competition for scarce resources. Specifically, we show that specialists became more desirable collaborators when the pace of change was faster, but when the pace of change was slower, generalists were more sought after as collaborators. Overall, our results highlight trade-offs associated with specialization for creative performance