Rescaling Biology: Increasing Integration Across Biological Scales and Subdisciplines to Enhance Understanding and Prediction

2021 ◽  
Author(s):  
Colette St. Mary ◽  
Thomas H Q Powell ◽  
John S Kominoski ◽  
Emily Weinert
Keyword(s):  
Multiple Scales ◽  
Genomic Variation ◽  
Biological Processes ◽  
Explicit Integration ◽  
Fully Integrated ◽  
Community Or ◽  
Complex Processes ◽  
Spatiotemporal Scales ◽  
Patterns And Processes ◽  
Vast Range

Synopsis The organization of the living world covers a vast range of spatiotemporal scales, from molecules to the biosphere, seconds to centuries. Biologists working within specialized subdisciplines tend to focus on different ranges of scales. Therefore, developing frameworks that enable testing questions and predictions of scaling requires sufficient understanding of complex processes across biological subdisciplines and spatiotemporal scales. Frameworks that enable scaling across subdisciplines would ideally allow us to test hypotheses about the degree to which explicit integration across spatiotemporal scales is needed for predicting the outcome of biological processes. For instance, how does genomic variation within populations allow us to explain community structure? How do the dynamics of cellular metabolism translate to our understanding of whole-ecosystem metabolism? Do patterns and processes operate seamlessly across biological scales, or are there fundamental laws of biological scaling that limit our ability to make predictions from one scale to another? Similarly, can sub-organismal structures and processes be sufficiently understood in isolation of potential feedbacks from the population, community, or ecosystem levels? And can we infer the sub-organismal processes from data on the population, community, or ecosystem scale? Concerted efforts to develop more cross-disciplinary frameworks will open doors to a more fully integrated field of biology. In this paper, we discuss how we might integrate across scales, specifically by (1) identifying scales and boundaries, (2) determining analogous units and processes across scales, (3) developing frameworks to unite multiple scales, and (4) extending frameworks to new empirical systems.

scholarly journals Multiscale low-dimensional motor cortical state dynamics predict naturalistic reach-and-grasp behavior

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hamidreza Abbaspourazad ◽  
Mahdi Choudhury ◽  
Yan T. Wong ◽  
Bijan Pesaran ◽  
Maryam M. Shanechi
Keyword(s):  
Neural Control ◽  
Multiple Scales ◽  
Network Activity ◽  
Neural Dynamics ◽  
Population Activity ◽  
Reach And Grasp ◽  
Spatiotemporal Scales ◽  
Motor Cortical ◽  
Low Dimensional ◽  
Low Dimensional Dynamics

AbstractMotor function depends on neural dynamics spanning multiple spatiotemporal scales of population activity, from spiking of neurons to larger-scale local field potentials (LFP). How multiple scales of low-dimensional population dynamics are related in control of movements remains unknown. Multiscale neural dynamics are especially important to study in naturalistic reach-and-grasp movements, which are relatively under-explored. We learn novel multiscale dynamical models for spike-LFP network activity in monkeys performing naturalistic reach-and-grasps. We show low-dimensional dynamics of spiking and LFP activity exhibited several principal modes, each with a unique decay-frequency characteristic. One principal mode dominantly predicted movements. Despite distinct principal modes existing at the two scales, this predictive mode was multiscale and shared between scales, and was shared across sessions and monkeys, yet did not simply replicate behavioral modes. Further, this multiscale mode’s decay-frequency explained behavior. We propose that multiscale, low-dimensional motor cortical state dynamics reflect the neural control of naturalistic reach-and-grasp behaviors.

scholarly journals Genomics of host-pathogen interactions: challenges and opportunities across ecological and spatiotemporal scales

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8013 ◽  
Author(s):  
Kathrin Näpflin ◽  
Emily A. O’Connor ◽  
Lutz Becks ◽  
Staffan Bensch ◽  
Vincenzo A. Ellis ◽  
...  
Keyword(s):  
Multiple Scales ◽  
Open Data ◽  
Emerging Infectious Diseases ◽  
Host Pathogen Interactions ◽  
Ecological Scales ◽  
Host Pathogen ◽  
Challenges And Opportunities ◽  
Spatiotemporal Scales ◽  
Data Granularity ◽  
The Impact

Evolutionary genomics has recently entered a new era in the study of host-pathogen interactions. A variety of novel genomic techniques has transformed the identification, detection and classification of both hosts and pathogens, allowing a greater resolution that helps decipher their underlying dynamics and provides novel insights into their environmental context. Nevertheless, many challenges to a general understanding of host-pathogen interactions remain, in particular in the synthesis and integration of concepts and findings across a variety of systems and different spatiotemporal and ecological scales. In this perspective we aim to highlight some of the commonalities and complexities across diverse studies of host-pathogen interactions, with a focus on ecological, spatiotemporal variation, and the choice of genomic methods used. We performed a quantitative review of recent literature to investigate links, patterns and potential tradeoffs between the complexity of genomic, ecological and spatiotemporal scales undertaken in individual host-pathogen studies. We found that the majority of studies used whole genome resolution to address their research objectives across a broad range of ecological scales, especially when focusing on the pathogen side of the interaction. Nevertheless, genomic studies conducted in a complex spatiotemporal context are currently rare in the literature. Because processes of host-pathogen interactions can be understood at multiple scales, from molecular-, cellular-, and physiological-scales to the levels of populations and ecosystems, we conclude that a major obstacle for synthesis across diverse host-pathogen systems is that data are collected on widely diverging scales with different degrees of resolution. This disparity not only hampers effective infrastructural organization of the data but also data granularity and accessibility. Comprehensive metadata deposited in association with genomic data in easily accessible databases will allow greater inference across systems in the future, especially when combined with open data standards and practices. The standardization and comparability of such data will facilitate early detection of emerging infectious diseases as well as studies of the impact of anthropogenic stressors, such as climate change, on disease dynamics in humans and wildlife.

Guns in the Hills: Firearms Circulation along the North-East Frontier of British India, 1860s–1910s

2021 ◽  
Vol 19 (4) ◽  
pp. 416-435
Author(s):  
Lipokmar Dzüvichü
Keyword(s):  
Multiple Scales ◽  
British India ◽  
Colonial State ◽  
Complex Processes ◽  
North East ◽  
The North ◽  
Imperial Expansion ◽  
Capital Access ◽  
And Diffusion

This article seeks to examine the significance of firearms in the making of the frontier and the ways in which societies on the North-East Frontier of British India encountered and adapted firearms between the 1860s and 1910s. It will study the complex ways in which the entry of firearms was mediated and galvanised by a range of processes such as imperial expansion, the intrusion of capital, access to resources, the role of violence, and the drawing of new borders. In turn, the circulation and diffusion of firearms also engendered a range of other practices and experiences among the societies on the frontier. Moving along various land and river routes, a range of individuals and traders were involved in circulating arms and ammunition into the imperial margins. They, in turn, linked the frontier geographies to markets, ports, and other larger oceanic networks. A focus on the flow of firearms as such illustrates a web of interconnections that straddled multiple scales and relations. As firearms circulated and gradually made their way into the periphery, various measures were initiated by the colonial state, such as enforcing prohibitive laws and instituting surveillance structures to control and block the flow of firearms along the North-East Frontier. This article examines some of these complex processes, dynamics, and experiences that ensued through the circulation and diffusion of firearms on the North-East Frontier of British India.

scholarly journals Assessing Students' Ability to Trace Matter in Dynamic Systems in Cell Biology

2006 ◽  
Vol 5 (4) ◽  
pp. 323-331 ◽  
Author(s):  
Christopher D. Wilson ◽  
Charles W. Anderson ◽  
Merle Heidemann ◽  
John E. Merrill ◽  
Brett W. Merritt ◽  
...  
Keyword(s):  
Dynamic Systems ◽  
Cell Biology ◽  
Instructional Strategy ◽  
Cellular Respiration ◽  
Diagnostic Tools ◽  
Biological Processes ◽  
College Level ◽  
Multiple Choice Questions ◽  
Complex Processes ◽  
Learning To Reason

College-level biology courses contain many complex processes that are often taught and learned as detailed narratives. These processes can be better understood by perceiving them as dynamic systems that are governed by common fundamental principles. Conservation of matter is such a principle, and thus tracing matter is an essential step in learning to reason about biological processes. We present here multiple-choice questions that measure students' ability and inclination to trace matter through photosynthesis and cellular respiration. Data associated with each question come from students in a large undergraduate biology course that was undergoing a shift in instructional strategy toward making fundamental principles (such as tracing matter) a central theme. We also present findings from interviews with students in the course. Our data indicate that 1) many students are not using tracing matter as a tool to reason about biological processes, 2) students have particular difficulties tracing matter between systems and have a persistent tendency to interconvert matter and energy, and 3) instructional changes seem to be effective in promoting application of the tracing matter principle. Using these items as diagnostic tools allows instructors to be proactive in addressing students' misconceptions and ineffective reasoning.

scholarly journals Genomics of hosts-pathogen interactions: challenges and opportunities across ecological and spatiotemporal scales

2019 ◽  
Author(s):  
Kathrin Näpflin ◽  
Lutz Becks ◽  
Staffan Bensch ◽  
Vincenzo A Ellis ◽  
Nina Hafer-Hahmann ◽  
...  
Keyword(s):  
Multiple Scales ◽  
Open Data ◽  
Emerging Infectious Diseases ◽  
Host Pathogen Interactions ◽  
Ecological Scales ◽  
Host Pathogen ◽  
Challenges And Opportunities ◽  
Spatiotemporal Scales ◽  
Data Granularity ◽  
The Impact

Evolutionary genomics has recently entered a new era in the study of host-pathogen interactions. A variety of novel genomic techniques has transformed to the identification, detection and classification of both hosts and pathogens, allowing a greater resolution that helps decipher their underlying dynamics and provides novel insights into their environmental context. Nevertheless, many challenges to a general understanding of host-pathogen interactions remain, in particular in the synthesis and integration of concepts and findings across a variety of systems and different spatiotemporal and ecological scales. In this perspective we aim to highlight some of the commonalities and complexities across diverse studies of host-pathogen interactions, with a focus on ecological, spatiotemporal variation, and the choice of genomic methods used. We performed a quantitative review of recent literature to investigate links, patterns and potential tradeoffs between the complexity of genomic, ecological and spatiotemporal scales undertaken in individual host-pathogen studies. We found that the majority of studies used whole genome resolution to address their research objectives across a broad range of ecological scales, especially when focusing on the pathogen side of the interaction. Nevertheless, genomic studies conducted in a complex spatiotemporal context are currently rare in the literature. Because processes of host-pathogen interactions can be understood at multiple scales, from molecular-, cellular-, and physiological-scales to the levels of populations and ecosystems, we conclude that a major obstacle for synthesis across diverse host-pathogen systems is that data are collected on widely diverging scales with different degrees of resolution. This disparity not only hampers effective infrastructural organization of the data but also data granularity and accessibility. Comprehensive metadata deposited in association with genomic data in easily accessible databases will allow greater inference across systems in the future, especially when combined with open data standards and practices. The standardization and comparability of such data will facilitate early detection of emerging infectious diseases as well as studies of the impact of anthropogenic stressors, such as climate change, on disease dynamics in humans and wildlife.

scholarly journals Characterization of systemic genomic instability in budding yeast

2020 ◽  
Author(s):  
Nadia M. V. Sampaio ◽  
V. P. Ajith ◽  
Ruth A. Watson ◽  
Lydia R. Heasley ◽  
Parijat Chakraborty ◽  
...  
Keyword(s):  
Experimental Model ◽  
Genomic Instability ◽  
Loss Of Heterozygosity ◽  
Time Window ◽  
Budding Yeast ◽  
Mutation Accumulation ◽  
Genomic Variation ◽  
Biological Processes ◽  
Whole Genome Analysis ◽  
Structural Genomic

ABSTRACTConventional models of genome evolution are centered around the principle that mutations form independently of each other and build up slowly over time. We characterized the occurrence of bursts of genome-wide loss-of-heterozygosity (LOH) in Saccharomyces cerevisiae, providing support for an additional non-independent and faster mode of mutation accumulation. We initially characterized a yeast clone isolated for carrying an LOH event at a specific chromosome site, and surprisingly, found that it also carried multiple unselected rearrangements elsewhere in its genome. Whole genome analysis of over 100 additional clones selected for carrying primary LOH tracts revealed that they too contained unselected structural alterations more often than control clones obtained without any selection. We also measured the rates of coincident LOH at two different chromosomes and found that double LOH formed at rates 14-150 fold higher than expected if the two underlying single LOH events occurred independently of each other. These results were consistent across different strain backgrounds, and in mutants incapable of entering meiosis. Our results indicate that a subset of mitotic cells within a population can experience discrete episodes of systemic genomic instability, when the entire genome becomes vulnerable and multiple chromosomal alterations can form over a narrow time window. They are reminiscent of early reports from the classic yeast genetics literature, as well as recent studies in humans, both in the cancer and genomic disorder contexts. The experimental model we describe provides a system to further dissect the fundamental biological processes responsible for punctuated bursts of structural genomic variation.SIGNIFICANCE STATEMENTMutations are generally thought to accumulate independently and gradually over many generations. Here, we combined complementary experimental approaches in budding yeast to track the appearance of chromosomal changes resulting in loss-of-heterozygosity (LOH). In contrast to the prevailing model, our results provide evidence for the existence of a path for non-independent accumulation of multiple chromosomal alteration events over few generations. These results are analogous to recent reports of bursts of genomic instability in human cells. The experimental model we describe provides a system to further dissect the fundamental biological processes underlying such punctuated bursts of mutation accumulation.

scholarly journals Proteomic approaches to dissect platelet function: half the story

Blood ◽  
2006 ◽  
Vol 108 (13) ◽  
pp. 3983-3991 ◽  
Author(s):  
Dmitri V. Gnatenko ◽  
Peter L. Perrotta ◽  
Wadie F. Bahou
Keyword(s):  
Platelet Function ◽  
Metabolic Pathways ◽  
Genetic Diseases ◽  
Protein Profiling ◽  
Biological Processes ◽  
Functional Changes ◽  
Complex Processes ◽  
Profiling Techniques ◽  
Platelet Proteome ◽  
Platelet Proteomics

AbstractPlatelets play critical roles in diverse hemostatic and pathologic disorders and are broadly implicated in various biological processes that include inflammation, wound healing, and thrombosis. Recent progress in high-throughput mRNA and protein profiling techniques has advanced our understanding of the biological functions of platelets. Platelet proteomics has been adopted to decode the complex processes that underlie platelet function by identifying novel platelet-expressed proteins, dissecting mechanisms of signal or metabolic pathways, and analyzing functional changes of the platelet proteome in normal and pathologic states. The integration of transcriptomics and proteomics, coupled with progress in bioinformatics, provides novel tools for dissecting platelet biology. In this review, we focus on current advances in platelet proteomic studies, with emphasis on the importance of parallel transcriptomic studies to optimally dissect platelet function. Applications of these global profiling approaches to investigate platelet genetic diseases and platelet-related disorders are also addressed.

scholarly journals Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only

2021 ◽  
Vol 9 ◽  
Author(s):  
Renato Assis Machado ◽  
Hercílio Martelli-Junior ◽  
Silvia Regina de Almeida Reis ◽  
Erika Calvano Küchler ◽  
Rafaela Scariot ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Cleft Lip ◽  
Ldl Receptor ◽  
Biological Processes ◽  
Complex Processes ◽  
Whole Exome ◽  
Novel Variants ◽  
Cleft Lip Palate

The identification of genetic risk factors for non-syndromic oral clefts is of great importance for better understanding the biological processes related to this heterogeneous and complex group of diseases. Herein we applied whole-exome sequencing to identify potential variants related to non-syndromic cleft palate only (NSCPO) in the multiethnic Brazilian population. Thirty NSCPO samples and 30 sex- and genetic ancestry-matched healthy controls were pooled (3 pools with 10 samples for each group) and subjected to whole-exome sequencing. After filtering, the functional affects, individually and through interactions, of the selected variants and genes were assessed by bioinformatic analyses. As a group, 399 variants in 216 genes related to palatogenesis/cleft palate, corresponding to 6.43%, were exclusively identified in the NSCPO pools. Among those genes are 99 associated with syndromes displaying cleft palate in their clinical spectrum and 92 previously related to cleft lip palate. The most significantly biological processes and pathways overrepresented in the NSCPO-identified genes were associated with the folic acid metabolism, highlighting the interaction between LDL receptor-related protein 6 (LRP6) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) that interconnect two large networks. This study yields novel data on characterization of specific variants and complex processes and pathways related to NSCPO, including many variants in genes of the folate/homocysteine pathway, and confirms that variants in genes related to syndromic cleft palate and cleft lip-palate may cause NSCPO.

scholarly journals Identification of a Cancer Stemness Driven Prognostic Model and Therapeutic Drug Targets by Machine Learning in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Mingchun Lai ◽  
Bin Xi ◽  
Shenyu Wei ◽  
Wenjin Zhang ◽  
Shusen Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Differential Expression Analysis ◽  
Genomic Variation ◽  
Gene Set Enrichment Analysis ◽  
Therapeutic Drug ◽  
Response Analysis ◽  
Therapeutic Effects ◽  
Biological Processes ◽  
Cancer Stemness

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies. Cancer stem cells (CSCs), characterized by self-renewal and drug-resistance, play an important role in the development and progression of diverse cancers, but the underlying association of HCC and CSCs is not fully researched.Methods: Transcriptome and clinical data of 903 patients in four independent HCC cohorts were obtained from TCGA, ICGC, and GEO databases. We evaluated the stemlike index for each patient to reflect the cancer stemness by using one-class logistic regression (OCLR) algorithm. GISTIC 2.0, Maftools and GSVA were used to reveal the association between the stemness index and genomic variation and biological processes in HCC. The differential expression analysis, univariate Cox analysis and LASSO analysis were used to identify the prognostic stemness signatures. The HCC stemness-related risk score (HCSRS) was constructed to quantify stemness levels of individual tumors. Based on HCSRS, the nomogram was established for HCC prognosis in a quantitative approach. Additionally, single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to evaluate the immune infiltration levels in HCC, and drug response analysis was adopted to identify potential agents with drug sensitivity in high-HCSRS score patients.Results: The stemness index in HCC tissues was significantly higher than that in normal tissues, and there was a significant positive correlation with pathological grade. Patients with high stemness index showed higher somatic mutation frequency, tumor mutation load, and copy number variation frequency, and were significantly enriched in tumor-related signaling pathways. Meanwhile, the 7-gene based HCSRS model that was trained and validated in 4 independent cohorts exhibited high predictive significance for overall survival (OS). Further analysis revealed that patients with high HCSRS possessed higher immunosuppression status, characterized by significantly decreased infiltration of anti-tumor immune cells (CD8 T cells, cytotoxic T cells, DC cells, NK cells, etc.) and exhausted CYT responses. At last, a total of twelve agents were identified to have potential therapeutic effects in high-HCSRS patients.Conclusion: In current study, we systematically analyzed the potential relationship of HCC stemness with genomic variation, tumor microenvironment and biological processes, provided a theoretical basis for individualized treatment of HCC patients.

scholarly journals Genomics of hosts-pathogen interactions: challenges and opportunities across ecological and spatiotemporal scales

2019 ◽  
Author(s):  
Kathrin Näpflin ◽  
Lutz Becks ◽  
Staffan Bensch ◽  
Vincenzo A Ellis ◽  
Nina Hafer-Hahmann ◽  
...  
Keyword(s):  
Multiple Scales ◽  
Open Data ◽  
Emerging Infectious Diseases ◽  
Host Pathogen Interactions ◽  
Ecological Scales ◽  
Host Pathogen ◽  
Challenges And Opportunities ◽  
Spatiotemporal Scales ◽  
Data Granularity ◽  
The Impact

Evolutionary genomics has recently entered a new era in the study of host-pathogen interactions. A variety of novel genomic techniques has transformed to the identification, detection and classification of both hosts and pathogens, allowing a greater resolution that helps decipher their underlying dynamics and provides novel insights into their environmental context. Nevertheless, many challenges to a general understanding of host-pathogen interactions remain, in particular in the synthesis and integration of concepts and findings across a variety of systems and different spatiotemporal and ecological scales. In this perspective we aim to highlight some of the commonalities and complexities across diverse studies of host-pathogen interactions, with a focus on ecological, spatiotemporal variation, and the choice of genomic methods used. We performed a quantitative review of recent literature to investigate links, patterns and potential tradeoffs between the complexity of genomic, ecological and spatiotemporal scales undertaken in individual host-pathogen studies. We found that the majority of studies used whole genome resolution to address their research objectives across a broad range of ecological scales, especially when focusing on the pathogen side of the interaction. Nevertheless, genomic studies conducted in a complex spatiotemporal context are currently rare in the literature. Because processes of host-pathogen interactions can be understood at multiple scales, from molecular-, cellular-, and physiological-scales to the levels of populations and ecosystems, we conclude that a major obstacle for synthesis across diverse host-pathogen systems is that data are collected on widely diverging scales with different degrees of resolution. This disparity not only hampers effective infrastructural organization of the data but also data granularity and accessibility. Comprehensive metadata deposited in association with genomic data in easily accessible databases will allow greater inference across systems in the future, especially when combined with open data standards and practices. The standardization and comparability of such data will facilitate early detection of emerging infectious diseases as well as studies of the impact of anthropogenic stressors, such as climate change, on disease dynamics in humans and wildlife.

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