bookmark | Chris Aldrich

🔖 Network medicine: a network-based approach to human disease | Albert-László Barabási, Natali Gulbahce & Joseph Loscalzo | Nature Reviews Genetics

Bookmarked Network medicine: a network-based approach to human disease by Albert-László Barabási, Natali Gulbahce & Joseph Loscalzo (Nature Reviews Genetics | volume 12, pages 56–68 (2011))

Abstract
Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular and intercellular network that links tissue and organ systems. The emerging tools of network medicine offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships among apparently distinct (patho)phenotypes. Advances in this direction are essential for identifying new disease genes, for uncovering the biological significance of disease-associated mutations identified by genome-wide association studies and full-genome sequencing, and for identifying drug targets and biomarkers for complex diseases.

Key points

A disease phenotype is rarely a consequence of an abnormality in a single effector gene product, but reflects various pathobiological processes that interact in a complex network.

Here we present an overview of the organizing principles that govern cellular networks and the implications of these principles for understanding disease. Network-based approaches have potential biological and clinical applications, from the identification of disease genes to better drug targets.

Whereas essential genes tend to be associated with hubs, or highly connected proteins, disease genes tend to segregate at the network's functional periphery, avoiding hubs.

Disease genes have a high propensity to interact with each other, forming disease modules. The identification of these disease modules can help us to identify disease pathways and predict other disease genes.

The highly interconnected nature of the interactome means that, at the molecular level, it is difficult to consider diseases as being independent of one another. The mapping of network-based dependencies between pathophenotypes has culminated in the concept of the diseasome, which represents disease maps whose nodes are diseases and whose links represent various molecular relationships between the disease-associated cellular components.

Diseases linked at the molecular level tend to show detectable comorbidity.

Network medicine has important applications to drug design, leading to the emergence of network pharmacology, and also in disease classification.

h/t Disconnected, fragmented, or united? a trans-disciplinary review of network science by César A. Hidalgo (Applied Network Science | SpringerLink)

🔖 A Dynamic Network Approach for the Study of Human Phenotypes | PLOS Computational Biology

Bookmarked A Dynamic Network Approach for the Study of Human Phenotypes by César A. Hidalgo , Nicholas Blumm, Albert-László Barabási, Nicholas A. Christakis (PLOS Computational Biology)

Author Summary: To help the understanding of physiological failures, diseases are defined as specific sets of phenotypes affecting one or several physiological systems. Yet, the complexity of biological systems implies that our working definitions of diseases are careful discretizations of a complex phenotypic space. To reconcile the discrete nature of diseases with the complexity of biological organisms, we need to understand how diseases are connected, as connections between these different discrete categories can be informative about the mechanisms causing physiological failures. Here we introduce the Phenotypic Disease Network (PDN) as a map summarizing phenotypic connections between diseases and show that diseases progress preferentially along the links of this map. Furthermore, we show that this progression is different for patients with different genders and racial backgrounds and that patients affected by diseases that are connected to many other diseases in the PDN tend to die sooner than those affected by less connected diseases. Additionally, we have created a queryable online database (http://hudine.neu.edu/) of the 18 different datasets generated from the more than 31 million patients in this study. The disease associations can be explored online or downloaded in bulk.

h/t Disconnected, fragmented, or united? a trans-disciplinary review of network science by César A. Hidalgo (Applied Network Science | SpringerLink)

🔖 Some Statistics of Evolution and Geographical Distribution in Plants and Animals, and their Significance by J.C. Willis & Udny Yule | Nature

Bookmarked Some Statistics of Evolution and Geographical Distribution in Plants and Animals, and their Significance by J. C. Willis and G. Udny Yule (Nature volume 109, pages 177–179)

Abstract
IN a paper read at the Linnean Society under the above title on February 2, the statistical methods long employed in “Age and Area” were pushed to their final conclusion. Age and area (review in Ann. of Bot., October, 1921, p. 493) is the name given to a principle gradually discovered in many years of work upon the flora of Ceylon, which, in brief, affirms that if one take groups of not less than ten allied species and compare them with similar groups allied to the first, the relative total areas occupied in a given country, or in the world, will be more or less proportional (whether directly or not we do not yet know) to their relative total ages, within that country or absolutely, as the case may be. The longer a group has existed the more area will it occupy. Tens are compared in order to eliminate chance differences as much as possible, and allied groups to avoid as far as may be the complications introduced by different ecological habit, etc. Herbs, for example, probably spread much more rapidly than trees, but both will obey Age and Area. It is of course obvious that age of itself cannot effect dispersal, but inasmuch as predictions as to distribution of species, occurrence of endemics, etc., can be successfully made upon the basis of age alone, it is clear that the average rate of spreading of a given species, and still more of a group of allied species, is very uniform, and therefore affords a measure of age. The result of the work is to show that in general the species (and genera) of smallest areas are the youngest, and are descended from the more widespread species that usually occur beside them.

h/t Disconnected, fragmented, or united? a trans-disciplinary review of network science by César A. Hidalgo (Applied Network Science | SpringerLink)

🔖 Equilibrium points in n-person games by John Nash | PNAS

Bookmarked Equilibrium points in n-person games by John F. Nash Jr. (PNAS 36 (1) 48-49; https://doi.org/10.1073/pnas.36.1.48)

One may define a concept of an n-person game in which each player has a finite set of pure strategies and in which a definite set of payments to the n players corresponds to each n-tuple of pure strategies, one strategy being taken for each player. For mixed strategies, which are probability distributions over the pure strategies, the pay-off functions are the expectations of the players, thus becoming polylinear forms in the probabilities with which the various players play their various pure strategies.

Any n-tuple of strategies, one for each player, may be regarded as a point in the product space obtained by multiplying the n strategy spaces of the players. One such n-tuple counters another if the strategy of each player in the countering n-tuple yields the highest obtainable expectation for its player against the n − 1 strategies of the other players in the countered n-tuple. A self-countering n-tuple is called an equilibrium point.

The correspondence of each n-tuple with its set of countering n-tuples gives a one-to-many mapping of the product space into itself. From the definition of countering we see that the set of countering points of a point is convex. By using the continuity of the pay-off functions we see that the graph of the mapping is closed. The closedness is equivalent to saying: if P1, P2, … and Q1, Q2, …, Qn, … are sequences of points in the product space where Qn → Q, Pn → P and Qn counters Pn then Q counters P.

Since the graph is closed and since the image of each point under the mapping is convex, we infer from Kakutani’s theorem1 that the mapping has a fixed point (i.e., point contained in its image). Hence there is an equilibrium point.

In the two-person zero-sum case the “main theorem”2 and the existence of an equilibrium point are equivalent. In this case any two equilibrium points lead to the same expectations for the players, but this need not occur in general.

Communicated by S. Lefschetz, November 16, 1949

🔖 Trust: The Social Virtues and The Creation of Prosperity by Francis Fukuyama

Bookmarked Trust: The Social Virtues and The Creation of Prosperity by Francis Fukuyama (Free Press)

In his bestselling The End of History and the Last Man, Francis Fukuyama argued that the end of the Cold War would also mean the beginning of a struggle for position in the rapidly emerging order of 21st-century capitalism. In Trust, a penetrating assessment of the emerging global economic order "after History," he explains the social principles of economic life and tells us what we need to know to win the coming struggle for world dominance. Challenging orthodoxies of both the left and right, Fukuyama examines a wide range of national cultures in order to divine the underlying principles that foster social and economic prosperity. Insisting that we cannot divorce economic life from cultural life, he contends that in an era when social capital may be as important as physical capital, only those societies with a high degree of social trust will be able to create the flexible, large-scale business organizations that are needed to compete in the new global economy. A brilliant study of the interconnectedness of economic life with cultural life, Trust is also an essential antidote to the increasing drift of American culture into extreme forms of individualism, which, if unchecked, will have dire consequences for the nation's economic health.

h/t Disconnected, fragmented, or united? a trans-disciplinary review of network science by César A. Hidalgo (Applied Network Science | SpringerLink)

Given the large number of “Trust” and “Truth” related books being released this year, most in reference to Donald J. Trump’s administration, this might be an interesting read which takes him out of the equation and potentially better underlines the bigger problem we’re seeing in a growing anti-scientific leaning America?

🔖 OpenStax

Bookmarked OpenStax (OpenStax)

Access our free college textbooks and low-cost learning materials.

👓 Hypothes.is Collector | John Stewart

Bookmarked Hypothes.is Collector by John Stewart (John Stewart)

In order to make it easier to track activity in Hypothes.is, I created a program called Hypothes.is Collector. The idea is that you can type in user name, a URL, a tag, or a group ID and click the button to see all of the related annotations. The program will create a new sheet with an archive of up to 200 annotations based on the search terms. It will then create a third sheet that will count how many of these annotations were made on each URL in the set by each user.

This seems like it could be an interesting tool for annotations in a classroom setting and is related to some of the broader Hypothes.is API tools.

cc: Greg McVerry, W. Ian O’Bryne

🔖 Write, Right? Write! – TRU Writer

Bookmarked Tru Writer by Alan Levine (https://splot.ca/writer/write)

Welcome to a new experiment in simple but elegant web publishing. This site let’s you quickly publish full formatted and media rich articles, essays, papers — without requiring any logins or tracking of personal information. Don’t take our word for it, explore one piece published here, chosen at random.

A published work includes a header image which you can upload to the TRU Writer. Choose how you wish to credit yourself as an author, or choose to by anonymous.

You should be able to copy the contents of anything you have written in a Word Processor, or already published on a web page, paste it into the TRU Writer editor. Most standard formatting (headers, bold, italic, underline, lists, blockquotes, hypertext links) will be preserved.

You can then edit/augment your work using a rich text editor, including embedding content from social media sites, and you can upload new images to be included within the text of your writing.

So find an essay or article and see what you can do with it by publishing online with the TRU Writer.

Give it a try now!

This is implemented as a WordPress theme, so it can be created for many different sites. Learn more about TRU Writer and where to find the theme.