Filogenômica levando em conta a homologia em escalas de gigabase

quinta-feira, junho 22, 2017

Homology-Aware Phylogenomics at Gigabase Scales

M. J. Sanderson Marius Nicolae M. M. McMahon

Syst Biol (2017) 66 (4): 590-603. DOI: https://doi.org/10.1093/sysbio/syw104

Published: 25 January 2017 Article history

Received: 19 May 2016 Revision Received: 31 October 2016

Accepted: 25 November 2016



Abstract

Obstacles to inferring species trees from whole genome data sets range from algorithmic and data management challenges to the wholesale discordance in evolutionary history found in different parts of a genome. Recent work that builds trees directly from genomes by parsing them into sets of small 

k-mer strings holds promise to streamline and simplify these efforts, but existing approaches do not account well for gene tree discordance. We describe a “seed and extend” protocol that finds nearly exact matching sets of orthologous k-mers and extends them to construct data sets that can properly account for genomic heterogeneity. Exploiting an efficient suffix array data structure, sets of whole genomes can be parsed and converted into phylogenetic data matrices rapidly, with contiguous blocks of k-mers from the same chromosome, gene, or scaffold concatenated as needed. Phylogenetic trees constructed from highly curated rice genome data and a diverse set of six other eukaryotic whole genome, transcriptome, and organellar genome data sets recovered trees nearly identical to published phylogenomic analyses, in a small fraction of the time, and requiring many fewer parameter choices. Our method’s ability to retain local homology information was demonstrated by using it to characterize gene tree discordance across the rice genome, and by its robustness to the high rate of interchromosomal gene transfer found in several rice species.

FREE PDF GRATIS: Syst Biol

Psiu! O genoma humano não foi totalmente sequenciado!!!

Psst, the human genome was never completely sequenced. Some scientists say it should be

By SHARON BEGLEY @sxbegle JUNE 20, 2017


The feat made headlines around the world: “Scientists Say Human Genome is Complete,” the New York Times announced in 2003. “The Human Genome,” the journals Science and Nature said in identical ta-dah cover lines unveiling the historic achievement.

There was one little problem.
“As a matter of truth in advertising, the ‘finished’ sequence isn’t finished,” said Eric Lander, who led the lab at the Whitehead Institute that deciphered more of the genome for the government-funded Human Genome Project than any other. “I always say ‘finished’ is a term of art.”
“It’s very fair to say the human genome was never fully sequenced,” Craig Venter, another genomics luminary, told STAT.
“The human genome has not been completely sequenced and neither has any other mammalian genome as far as I’m aware,” said Harvard Medical School bioengineer George Church, who made key early advances in sequencing technology.
What insiders know, however, is not well-understood by the rest of us, who take for granted that each A, T, C, and G that makes up the DNA of all 23 pairs of human chromosomes has been completely worked out. When scientists finished the first draft of the human genome, in 2001, and again when they had the final version in 2003, no one lied, exactly. FAQs from the National Institutes of Health refer to the sequence’s “essential completion,” and to the question, “Is the human genome completely sequenced?” they answer, “Yes,” with the caveat — that it’s “as complete as it can be” given available technology.
Perhaps nobody paid much attention because the missing sequences didn’t seem to matter. But now it appears they may play a role in conditions such as cancer and autism.
“A lot of people in the 1980s and 1990s [when the Human Genome Project was getting started] thought of these regions as nonfunctional,” said Karen Miga, a molecular biologist at the University of California, Santa Cruz. “But that’s no longer the case.” Some of them, called satellite regions, misbehave in some forms of cancer, she said, “so something is going on in these regions that’s important.”
Miga regards them as the explorer Livingstone did Africa — terra incognita whose inaccessibility seems like a personal affront. Sequencing the unsequenced, she said, “is the last frontier for human genetics and genomics.”
Church, too, has been making that point, mentioning it at both the May meeting of an effort to synthesize genomes, and at last weekend’s meeting of the International Society for Stem Cell Research. Most of the unsequenced regions, he said, “have some connection to aging and aneuploidy” (an abnormal number of chromosomes such as what occurs in Down syndrome). Church estimates 4 percent to 9 percent of the human genome hasn’t been sequenced. Miga thinks it’s 8 percent.
The reason for these gaps is that DNA sequencing machines don’t read genomes like humans read books, from the first word to the last. Instead, they first randomly chop up copies of the 23 pairs of chromosomes, which total some 3 billion “letters,” so the machines aren’t overwhelmed. The resulting chunks contain from 1,000 letters (during the Human Genome Project) to a few hundred (in today’s more advanced sequencing machines). The chunks overlap. Computers match up the overlaps, assembling the chunks into the correct sequence.
...
Read more here/Leia mais aquiSTAT

Filmada a replicação do DNA pela primeira vez: não é o que era esperado!

quarta-feira, junho 21, 2017

Independent and Stochastic Action of DNA Polymerases in the Replisome

James E. Graham3, Kenneth J. Marians , Stephen C. Kowalczykowski4

3Present address: Oxford Nanopore Technologies, Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, United Kingdom

4Lead Contact


Article Info

Publication History

Published: June 15, 2017 Accepted: May 26, 2017

Received in revised form: March 29, 2017 Received: November 9, 2016



Highlights

• Leading- and lagging-strand polymerases function autonomously within a replisome

• Replication is kinetically discontinuous and punctuated by pauses and rate-switches

• The helicase slows in a self-regulating fail-safe mechanism when synthesis pauses

• Priming is scaled to a 5-fold reduced processivity of the lagging-strand polymerase

Summary

It has been assumed that DNA synthesis by the leading- and lagging-strand polymerases in the replisome must be coordinated to avoid the formation of significant gaps in the nascent strands. Using real-time single-molecule analysis, we establish that leading- and lagging-strand DNA polymerases function independently within a single replisome. Although average rates of DNA synthesis on leading and lagging strands are similar, individual trajectories of both DNA polymerases display stochastically switchable rates of synthesis interspersed with distinct pauses. DNA unwinding by the replicative helicase may continue during such pauses, but a self-governing mechanism, where helicase speed is reduced by ∼80%, permits recoupling of polymerase to helicase. These features imply a more dynamic, kinetically discontinuous replication process, wherein contacts within the replisome are continually broken and reformed. We conclude that the stochastic behavior of replisome components ensures complete DNA duplication without requiring coordination of leading- and lagging-strand synthesis.

FREE PDF GRATIS: Cell

Uma grande família de genes passa a perna em Mendel



Heredity: The gene family that cheats Mendel

J Dylan Shropshire Antonis Rokas 

Vanderbilt University, United States

INSIGHT Jun 20, 2017


Abstract

Some alleles of the wtf gene family can increase their chances of spreading by using poisons to kill other alleles, and antidotes to save themselves.

FREE PDF GRATIS: Heredity

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A large gene family in fission yeast encodes spore killers that subvert Mendel’s law

Wen Hu Zhao-Di Jiang Fang Suo Jin-Xin Zheng Wan-Zhong He Li-Lin Du 

National Institute of Biological Sciences, China Tsinghua University, China

RESEARCH ARTICLE Jun 20, 2017

Abstract

Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve.


eLife digest

During evolution, new species emerge when individuals from different populations of similar organisms no longer breed with each other, or when the offspring produced if they do breed are sterile. This process is known as “reproductive isolation” and, for over 100 years, evolutionary biologists have tried to better understand how this process happens.

Animals, plants and fungi produce sex cells – known as gametes – when they are preparing to reproduce. These cells are made when cells containing two copies of every gene in the organism divide to produce new cells that each only have one copy of each gene. Therefore, a particular gene copy usually has a 50% chance of being carried by an individual gamete. There are genes that selfishly increase their chances of being transmitted to the next generation by destroying the gametes that do not carry them. These “gamete killer” genes reduce the fertility of the organism and lead to reproductive isolation.

Fission yeast is a fungus that is widely used in research. There are different strains of fission yeast that are reproductively isolated from each other, but it is not known whether gamete killers are responsible for this isolation. To address this question, Hu et al. investigated the causes of reproductive isolation in fission yeast.

The experiments identified two gamete killers, referred to as cw9 and cw27. Both genes belong to the wtf gene family. Each gene is believed to encode two different proteins, one that acts as a poison and one that acts as an antidote. The poison is capable of killing all gametes, but the antidote protects the cells that contain the gamete killer gene. Further experiments show that the antidote produced by one of the gamete killer genes cannot protect cells against the poison produced by the other gene.

A separate study by Nuckolls et al. found that another member of the wtf family also acts as a gamete killer in fission yeast. Together, these findings shed new light on the causes of reproductive isolation, and will contribute to deeper understanding of speciation and evolution in general.


FREE PDF GRATIS: Heredity Figures

Um manifesto a favor da ciência reprodutível

terça-feira, junho 20, 2017

A manifesto for reproducible science

Marcus R. Munafò, Brian A. Nosek, Dorothy V. M. Bishop, Katherine S. Button, Christopher D. Chambers, Nathalie Percie du Sert, Uri Simonsohn, Eric-Jan Wagenmakers, Jennifer J. Ware & John P. A. Ioannidis

Nature Human Behaviour 1, Article number: 0021 (2017)


Download Citation

Social sciences

Published online: 10 January 2017


Figure 1: Threats to reproducible science.

Abstract

Improving the reliability and efficiency of scientific research will increase the credibility of the published scientific literature and accelerate discovery. Here we argue for the adoption of measures to optimize key elements of the scientific process: methods, reporting and dissemination, reproducibility, evaluation and incentives. There is some evidence from both simulations and empirical studies supporting the likely effectiveness of these measures, but their broad adoption by researchers, institutions, funders and journals will require iterative evaluation and improvement. We discuss the goals of these measures, and how they can be implemented, in the hope that this will facilitate action toward improving the transparency, reproducibility and efficiency of scientific research.

What proportion of published research is likely to be false? Low sample size, small effect sizes, data dredging (also known as P-hacking), conflicts of interest, large numbers of scientists working competitively in silos without combining their efforts, and so on, may conspire to dramatically increase the probability that a published finding is incorrect1. The field of metascience — the scientific study of science itself — is flourishing and has generated substantial empirical evidence for the existence and prevalence of threats to efficiency in knowledge accumulation (refs 2,3,4,5,6,7; Fig. 1).

Acknowledgements

M.R.M. is a member of the UK Centre for Tobacco Control Studies, a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. This work was supported by the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/6). D.V.M.B. is funded by a Wellcome Trust Principal Research Fellowship and Programme (grant number 082498/Z/07/Z). N.P.d.S. is employed by the NC3Rs, which is primarily funded by the UK government. J.P.A.I. is funded by an unrestricted gift from S. O'Donnell and B. O'Donnell to the Stanford Prevention Research Center. METRICS is supported by a grant by the Laura and John Arnold Foundation. The authors are grateful to Don van den Bergh for preparing Fig. 2.

Author information

Affiliations

MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.

Marcus R. Munafò
UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, UK.

Marcus R. Munafò
Department of Psychology, University of Virginia, Charlottesville, Virginia 22904, USA.

Brian A. Nosek
Center for Open Science, Charlottesville, Virginia 22903, USA.

Brian A. Nosek
Department of Experimental Psychology, University of Oxford, 9 South Parks Road, Oxford OX1 3UD, UK.

Dorothy V. M. Bishop
Department of Psychology, University of Bath, Bath BS2 7AY, UK.

Katherine S. Button
Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF24 4HQ, UK.

Christopher D. Chambers
National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London NW1 2BE, UK.

Nathalie Percie du Sert
The Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Uri Simonsohn
Department of Psychology, University of Amsterdam, Amsterdam 1018 WT, Netherlands.

Eric-Jan Wagenmakers
CHDI Management/CHDI Foundation, New York, New York 10001, USA.

Jennifer J. Ware
Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford 94304, California, USA.

John P. A. Ioannidis
Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford 94305, California, USA.

John P. A. Ioannidis
Department of Statistics, Stanford University School of Humanities and Sciences, Stanford 94305, California, USA.

John P. A. Ioannidis
Competing interests
M.R.M, together with C.D.C and D.V.M.B., has received funding from the BBSRC (grant number BB/N019660/1) to convene a workshop on advanced methods for reproducible science, and is chair of the CHDI Foundation Independent Statistical Standing Committee. B.A.N. is executive director of the non-profit Center for Open Science with a mission to increase openness, integrity and reproducibility of research. N.P.d.S. leads the NC3Rs programme of work on experimental design, which developed the ARRIVE guidelines and Experimental Design Assistant. J.J.W. is director, experimental design, at CHDI Management/CHDI Foundation, a non-profit biomedical research organization exclusively dedicated to developing therapeutics for Huntington's disease. The other authors declare no competing interests.

Corresponding author

Correspondence to Marcus R. Munafò.

FREE PDF GRATIS: Nature Human Behavior

EXTRA! EXTRA! EXTRA! A teoria do equilíbrio pontuado ressuscitou!!!

segunda-feira, junho 19, 2017

Punctuated evolution shaped modern vertebrate diversity

Michael J. Landis 1 and Joshua G. Schraiber 2, 3

1 Department of Ecology and Evolutionary Biology, Yale University

2 Department of Biology, Temple University

Institute for Genomics and Evolutionary Medicine, Temple University

June 16, 2017

Source/Fonte: Biobook


Abstract

The relative importance of different modes of evolution in shaping phenotypic diversity remains a hotly debated question. Fossil data suggest that stasis may be a common mode of evolution, while modern data suggest very fast rates of evolution. One way to reconcile these observations is to imagine that evolution is punctuated, rather than gradual, on geological time scales. To test this hypothesis, we developed a novel maximum likelihood framework for fitting L´evy processes to comparative morphological data. This class of stochastic processes includes both a gradual and punctuated component. We found that a plurality of modern vertebrate clades examined are best fit by punctuated processes over models of gradual change, gradual stasis, and adaptive radiation. When we compare our results to theoretical expectations of the rate and speed of regime shifts for models that detail fitness landscape dynamics, we find that our quantitative results are broadly compatible with both microevolutionary models and with observations from the fossil record.

FREE PDF GRATIS: bioRxiv 








http://biobook.kuensting.org/bb/evolution/speciation/1000px-Punctuated-equilibrium2.svg.png

O que conta como dados científicos?

What Counts as Scientific Data? A Relational Framework

Sabina Leonelli*,†



Abstract

This paper proposes an account of scientific data that makes sense of recent debates on data-driven and ‘big data’ research, while also building on the history of data production and use particularly within biology. In this view, ‘data’ is a relational category applied to research outputs that are taken, at specific moments of inquiry, to provide evidence for knowledge claims of interest to the researchers involved. They do not have truth-value in and of themselves, nor can they be seen as straightforward representations of given phenomena. Rather, they are fungible objects defined by their portability and prospective usefulness as evidence.

FREE PDF GRATIS: Philosophy of Science

Direcionando fótons solares para provisão sustentável de comida, energia, e água

sábado, junho 17, 2017

Directing solar photons to sustainably meet food, energy, and water needs

Emre Gençer, Caleb Miskin, Xingshu Sun, M. Ryyan Khan, Peter Bermel, M. Ashraf Alam & Rakesh Agrawal

Scientific Reports 7, Article number: 3133 (2017)


Download Citation

Chemical engineering Electrical and electronic engineering Energy harvesting Solar energy

Received: 20 December 2016 Accepted: 27 April 2017

Published online: 09 June 2017

Fig. 3: Conceptual implementation of SUFEWS in which photons are managed efficiently over crop/pasture land to simultaneously and harmoniously produce FEW products in a sustainable future for a Full Earth. (Figure credit: Pamela Burroff-Murr, Purdue University). 

Abstract

As we approach a “Full Earth” of over ten billion people within the next century, unprecedented demands will be placed on food, energy and water (FEW) supplies. The grand challenge before us is to sustainably meet humanity’s FEW needs using scarcer resources. To overcome this challenge, we propose the utilization of the entire solar spectrum by redirecting solar photons to maximize FEW production from a given land area. We present novel solar spectrum unbundling FEW systems (SUFEWS), which can meet FEW needs locally while reducing the overall environmental impact of meeting these needs. The ability to meet FEW needs locally is critical, as significant population growth is expected in less-developed areas of the world. The proposed system presents a solution to harness the same amount of solar products (crops, electricity, and purified water) that could otherwise require ~60% more land if SUFEWS were not used—a major step for Full Earth preparedness.

Acknowledgements

The authors thank Mark Koeper, Ryan Ellis, Pamela Burroff-Murr, and our agricultural collaborators for valuable inputs. Research was supported as part of the Center for Direct Catalytic Conversion of Biomass to Biofuels (C3Bio), an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Award DE-SC0000997, and Award DE-EE0004946 (PVMI Bay Area PV Consortium) and the National Science Foundation, under Solar Economy Integrative Education and Research Traineeship Program (IGERT) Grant 0903670-DGE and CAREER: Thermophotonics for Efficient Harvesting of Waste Heat as Electricity, Grant EEC1454315.

Author information

Affiliations

Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA

Emre Gençer, Caleb Miskin & Rakesh Agrawal

School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, 47907, USA

Xingshu Sun, M. Ryyan Khan, Peter Bermel & M. Ashraf Alam

Contributions

E.G., C.M. and R.A. designed research; E.G. and R.A. performed all systems calculations and MSF desalination simulations; X.S., M.R.K. and M.A.A. calculated maximum PV energy conversion efficiencies; P.B. calculated optimal operating temperatures; E.G., C.M., M.A.A., P.B. and R.A. analyzed data; E.G., C.M. and R.A. wrote the manuscript, all authors reviewed and approved the final version of the manuscript. R.A. directed the overall research.

Competing Interests

The authors declare that they have no competing interests.

Corresponding author

Correspondence to Rakesh Agrawal.

FREE PDF GRATIS: Scientific Reports Sup. Info.

Reinaldo José Lopes (Folha de São Paulo), atualize o upgrade Darwin 3.0: Três modos de evolução por seleção natural e deriva - uma nova ou ampliada síntese evolucionária?

Biological Theory

June 2017, Volume 12, Issue 2, pp 67–71

Three Modes of Evolution by Natural Selection and Drift: A New or an Extended Evolutionary Synthesis?

Authors

Authors and affiliations

Marion Blute1

Email author

View author's OrcID profile

1.Department of SociologyUniversity of TorontoTorontoCanada

Commentary

First Online: 07 April 2017


Cite this article as:

Blute, M. Biol Theory (2017) 12: 67. doi:10.1007/s13752-017-0264-8

Source/Fonte: Music of Life


Abstract

According to sources both in print and at a recent meeting, evolutionary theory is currently undergoing change which some would characterize as a New Synthesis, and others as an Extended Synthesis. This article argues that the important changes involve recognizing that there are three means by which evolutionary change can be initiated (genetically, ecologically, and developmentally) and three corresponding modes of evolutionary drift. It compares the three and goes on to discuss the scale of innovation and extended or inclusive and Lamarckian inheritance. It concludes from these that “new trends in evolutionary biology” are in part a new, and in part an extended evolutionary synthesis.

Keywords

Evolutionary drift Extended evolutionary synthesis Extended inheritance Lamarckian inheritance Lamarckian evolution New evolutionary synthesis

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Subscription or payment needed/Requer assinatura ou pagamento

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NOTA DESTE BLOGGER:

O artigo é mais uma tentativa de "controle de danos", que este blogger está vendo como um estilo pós-16 de Altenberg: há uma profunda crise epistemológica na teoria da evolução de Darwin através da seleção natural e n mecanismos evolucionários (de A a Z, vai que um falhe...) no contexto de justificação teórica, que seus defensores procuram juntar água (Darwin) e óleo (evidências enocntradas na natureza). Elas não se misturam, e em vez de reconhecerem o colapso epistêmico fragoroso de Darwin, seus defensores ficam enchendo linguiça nas publicações científicas.

Darwin morreu! Viva Darwin!!!

Stephen Hawking estava errado: espaço-tempo era infinito no Big Bang

sexta-feira, junho 16, 2017

Lorentzian quantum cosmology


Job Feldbrugge, Jean-Luc Lehners, and Neil Turok

Phys. Rev. D 95, 103508 – Published 16 May 2017


ABSTRACT

We argue that the Lorentzian path integral is a better starting point for quantum cosmology than its Euclidean counterpart. In particular, we revisit the minisuperspace calculation of the Feynman path integral for quantum gravity with a positive cosmological constant. Instead of rotating to Euclidean time, we deform the contour of integration over metrics into the complex plane, exploiting Picard-Lefschetz theory to transform the path integral from a conditionally convergent integral into an absolutely convergent one. We show that this procedure unambiguously determines which semiclassical saddle point solutions are relevant to the quantum mechanical amplitude. Imposing “no-boundary” initial conditions, i.e., restricting attention to regular, complex metrics with no initial boundary, we find that the dominant saddle contributes a semiclassical exponential factor which is precisely the inverse of the famous Hartle-Hawking result.

Received 22 March 2017


© 2017 American Physical Society

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FREE PDF GRATIS: arXiv

Cientistas descobrem mais complexidade no cérebro - 11 estruturas dimensionais: mero acaso, fortuita necessidade ou design inteligente?

Front. Comput. Neurosci., 12 June 2017 


Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function

Michael W. Reimann1†, Max Nolte1†, Martina Scolamiero2, Katharine Turner2, Rodrigo Perin3, Giuseppe Chindemi1, Paweł Dłotko4‡, Ran Levi5‡, Kathryn Hess2*‡ and Henry Markram1,3*‡

1Blue Brain Project, École Polytechnique Fédérale de Lausanne, Geneva, Switzerland

2Laboratory for Topology and Neuroscience, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

3Laboratory of Neural Microcircuitry, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

4DataShape, INRIA Saclay, Palaiseau, France

5Institute of Mathematics, University of Aberdeen, Aberdeen, United Kingdom

Source/Fonte: Psychology Today

The lack of a formal link between neural network structure and its emergent function has hampered our understanding of how the brain processes information. We have now come closer to describing such a link by taking the direction of synaptic transmission into account, constructing graphs of a network that reflect the direction of information flow, and analyzing these directed graphs using algebraic topology. Applying this approach to a local network of neurons in the neocortex revealed a remarkably intricate and previously unseen topology of synaptic connectivity. The synaptic network contains an abundance of cliques of neurons bound into cavities that guide the emergence of correlated activity. In response to stimuli, correlated activity binds synaptically connected neurons into functional cliques and cavities that evolve in a stereotypical sequence toward peak complexity. We propose that the brain processes stimuli by forming increasingly complex functional cliques and cavities.

Author Contributions

HM and RL developed and initially conceived the study over 10 years of discussions. HM, RL, and KH conceived and directed the final study. KH and RL directed the applicability of concepts in algebraic topology to neuroscience. HM directed the relevance of algebraic topology in neuroscience. The Blue Brain Project team reconstructed the microcircuit and developed the capability to simulate the activity. MN performed the simulations. MN, MR, and PD generated the directed flag complexes from the connection matrices for analysis. KH and RL developed the theory for directed cliques and directed simplicial complexes. MR and RL developed the definition of directionality within motifs and directed cliques. MR developed the definition for transmission response matrices. PD developed the code to isolate simplices and directed simplices and performed initial computations. MS performed topological and statistical analyses on the flag complexes and on the C. elegans connectome. KT helped with initial statistical analysis of network responses to stimuli. MR and MN analyzed the simulation data, mapped it onto the topological data and generated the figures. RP performed the patch-clamp experiments. GC and MR performed the corresponding in silico experiments. HM, KH, RL, MR, and MN wrote the paper.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

This work was supported by funding from the ETH Domain for the Blue Brain Project and the Laboratory of Neural Microcircuitry. The Blue Brain Project's IBM BlueGene/Q system, BlueBrain IV, is funded by the ETH Board and hosted at the Swiss National Supercomputing Center (CSCS). MS was supported by the NCCR Synapsy grant of the Swiss National Science Foundation. Partial support for PD was provided by the GUDHI project, supported by an Advanced Investigator Grant of the European Research Council and hosted by INRIA. We thank Eilif Muller for providing input on the analysis, Magdalena Kedziorek for help with proving maximality in directed cliques, Gard Spreemann for help with the analysis of the C. elegans connectome, and Taylor H. Newton for helpful discussions about statistical methods.

Supplementary Material

The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fncom.2017.00048/full#supplementary-material

FREE PDF GRATIS: Front. Comput. Neurosci.