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This report provides a global view of how gene expression is affected by DNA replication. We analyzed synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression. We use a higher‐order singular value decomposition to integrate the global mRNA expression measured in the multiple time courses, detect and remove experimental artifacts and identify significant combinations of patterns of expression variation across the genes, time points and conditions. We find that, first, ∼88% of the global mRNA expression is independent of DNA replication. Second, the requirement of DNA replication for efficient histone gene expression is independent of conditions that elicit DNA damage checkpoint responses. Third, origin licensing decreases the expression of genes with origins near their 3′ ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation. In this first global view of how DNA replication affects transcription, ∼88% of global gene expression is found to be independent of DNA replication, significantly lowering the recently measured upper bound to replication‐dependent mRNA expression. The requirement of DNA replication for efficient histone gene expression is found to be independent of conditions that elicit DNA damage checkpoint responses. Origin licensing is found to decrease expression of genes with origins near their 3′ ends, experimentally revealing for the first time that downstream origins can regulate the expression of upstream genes, and demonstrating that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation. The recent analogy of the tensor higher‐order singular value decomposition (HOSVD) with the matrix singular value decomposition (SVD), which already enables the interpretation of the HOSVD in terms of the cellular states, biological processess and experimental artifacts that compose the data tensor, is extended by mathematically defining the operation of HOSVD data reconstruction, and by computationally using this operation to remove experimental artifacts from the data.

IntroductionThe aftermath of stroke leaves many consequences including cognitive deficits and falls due to imbalance. Stroke survivors and families struggle to navigate the complex healthcare system with little assistance posthospital discharge, often leading to early hospital readmission and worse stroke outcomes. Telemedicine Guided Education on Secondary Stroke and Fall Prevention Following Inpatient Rehabilitation feasibility study examines whether stroke survivors and their caregivers find value in telerehabilitation (TR) home visits that provide individualised care and education by a multidisciplinary team after discharge from inpatient rehabilitation.Methods and analysisA prospective, single arm, pilot study is designed to evaluate the feasibility of weekly TR home visits initiated postdischarge from inpatient rehabilitation. Newly diagnosed patients with stroke are recruited from a Houston-based comprehensive stroke centre inpatient rehabilitation unit, loaned an iPad with data plan and trained to use information technology security-approved videoconferencing application. After hospital discharge, six weekly TR home visits are led by rotating specialists (pharmacist, physical/occupational therapist, speech therapist, rehabilitation physician, social worker, geriatrician specialised in fracture prevention) followed by satisfaction survey on week 7. Specialists visually assess patients in real time, educate them on secondary stroke and fall prevention and suggest ways to improve function including direct medical interventions when indicated. Primary outcomes are proportion of eligible patients consenting to the study, participation rate in all six TR home visits and satisfaction score. The study started 31 December 2015 with plan to enrol up to 50 patients over 24 months. Feasibility study results will inform us as to whether a randomised controlled trial is warranted to determine efficacy of TR home visit intervention in improving stroke outcomes.Ethics and disseminationEthics approval obtained by the Institutional Review Board (IRB), Committee for the Protection of Human Subjects, IRB number: HSC-MS-14–0994. Study results will be submitted for publication in a peer-reviewed journal.