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<html> <head>
<br>
<br>
<p>
<p>
<title>Mike Duff</title>
</head>
<body bgcolor="#445544" text=#99AA99 link=#DD7711 vlink=#DD7711 alink=#DD7711>
<font face='helvetica'>
<TABLE>
<TR><TD width="10%"><TD width=600>
<!-- <img src = "thinking_about_computational_genomics_in_leucadia.jpg" width="300" height="200">
<img src = "duff_labphoto1.jpg" width="300" height="200">
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<h3>Michael Duff</h3>
Assistant Professor in Residence<br>
<a href="http://genetics.uchc.edu">
Department of Genetics and Genome Sciences</a><br>
UConn Health Center<br>
Institute for Systems Genomics<br>
University of Connecticut<br>
400 Farmington Ave<br>
Farmington CT 06030<br>
<a href="mailto:moduff@gmail.com"><font color="#DD7711">moduff@gmail.com</font></a>
<p>
<font color="#FF0000">
***As of December 2018, I am with the Fred Hutchinson Cancer Research Center***
in sunny Seattle WA, conducting research on B-cell receptor repertoire dynamics
in response to infection and vaccination.<br>
</font>
<p>
<a href="moduff.github.io"><font color="#3399FF">moduff.github.io</font></a>
<p><em>
Research directions: Machine Learning,
Bioinformatics/Computational Biology/Computational Genomics, Reinforcement Learning Theory,
Bayesian methods, Applied Statistics/Mathematics,
AI, Deep-Learning, Optimization and Operations Research.</em>
<!--
<a href="duff_cv_april_2019.pdf"> CV</a>
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<html> <head>
<br>
<br>
<p>
<p>
My efforts in the <a href="http://graveleylab.cam.uchc.edu/Graveley/index.html"> Graveley Lab</a>
have been directed toward bringing computational approaches, statistical modeling methods, and
bioinformatics tools to bear upon problems posed by the analysis of Next-Generation-Sequencing (NGS) data,
including the standard repertoire of techniques drawn from computational genomics: genome assembly, sequence alignment,
gene-expression analysis, motif finding, SNP and structural-variant detection, phylogenetic analysis,
and identification of regulatory sequences and networks---as well as the development of special-purpose
ad-hoc computational tools for particular applications and novel techniques for data visualization.
<p>
<ul>
<li>NGS data analysis<p>
<ul>
<li>DNA/RNA/ChIP/CLIP/iCLIP/RIP-seq data analysis(<a href="http://genome.ucsc.edu/ENCODE/">ENCODE</a>)<br><p>
<li>alternative splicing and recursive splicing in D.melanogaster (<a href="http://www.modencode.org/">modENCODE</a>, DSCAM)<br><p>
<li>RNA interactions and functional intronic domains<br><p>
<li>lincRNA data analysis in hES differentiation<br><p>
<li>Human genetic variation, GWAS, and psychogenetics<br><p>
<li>analysis of RNAi off-target effects<br><p>
<li>transplicing<br><p>
<li>Polyomavirus editing, transcript expression profiling for the virus and its host<br><p>
<!--
<li>transcription/splicing kinetic models<br><p>
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<li>alternative-splicing changes during Human embryonic stem cell differentiation<br><p>
<li>Archaeal CRISPR-Cas systems<br><p>
<!--
<li>Squid (<i>Loligo pealei</i>) genome assembly and RNA-editing analysis<br><p>
<li>Drosophila neurogenetics<br><p>
-->
</ul>
<li>machine learning methods <p>
<ul>
<li>Bayesian methods, model-structure induction, and deep learning, transformers, LLMs, & generative diffusion for (structural) biology<br><p>
<li>reinforcement learning theory<br><p>
<li>experimental design<br><p>
<li>sequential decision-making under uncertainty, bandit problems<br><p>
</ul>
<li>two new courses: <p>
<ul>
<li>MEDS 5325: <em>Bioinformatics Practicum</em> <p>
<li>MEDS 6498: <em>Machine Learning for Genomics</em> <p>
</ul>
<!--
<li>other inquisitions <p>
<ul>
<li>Monte-Carlo computation for gauging independence in very-large contingency tables<br><p>
<li>dynamic modelling of sepsis<br><p>
<li>subgraph isomorphism and spectral graph theory<br><p>
<li>analytic combinatorics<br><p>
</ul>
-->
</ul>
<br>
<p>
<br>
<p>
<br>
<font color="#FFCC00">
How can Next-Generation-Sequencing be used to infer causal relationships between transcribed elements? How
can ambiguity and bias be modeled and resolved?</font>
<br>
<p>
<br>
<img src = "computational_genomics_unit.jpg" width="500" height="250">
<br>
<p>
<h3>Papers</h3>
Willis, J.R. et al (2025). <a href = "https://www.science.org/doi/10.1126/science.adr8382">Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans</a>, Science 0,eadr8382DOI:10.1126/science.adr8382
<p>
Tom G. Caniels et al (2025). <a href = "https://www.science.org/doi/10.1126/science.adv5572">Precise targeting of HIV broadly neutralizing antibody precursors in humans</a>.Science 0,eadv5572DOI:10.1126/science.adv5572
<p>
Hahn, W.O. et al (2024). <a href = "https://doi.org/10.1101/2024.05.08.24306957">HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies</a>. medRxiv 2024.05.08.24306957
<p>
Cohen, K.W., et al (2021) <a href="https://www.medrxiv.org/content/10.1101/2021.08.23.21262508v1">Shared HIV envelope-specific B cell clonotypes induced by a pox-protein vaccine regimen</a>. medRxiv doi: https://doi.org/10.1101/2021.08.23.21262508
<p>
Mou, Y.,et al (2020) <a href="https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-020-01088-0">Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia</a>, Acta Neuropathologica Communications https://doi.org/10.1186/s40478-020-01088-0
<p>
Van Nostrand, E.L., et al (2020) <a href="https://www.nature.com/articles/s41586-020-2077-3">A Large-Scale Binding and Functional Map of Human RNA
Binding Proteins</a>, Nature 583, pp. 711–719, July 29.
<p>
Chang, H.H., Eibi, G., et al (2017) <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184455">Incidence of Pancreatic Cancer is Dramatically Increased by a
High Fat, High Calorie Diet in KrasG12D Mice</a>. PLoS ONE 12(9).
<p>
Pilling, L.C., et al (2017) <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185083">Red Blood Cell Distribution Width: genetic evidence for aging pathways
in 116,666 volunteers</a>. PLoS ONE 12(9).<p>
Garren, S., Duff, M.O., & Carmichael, G. (2015) <a href="http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005166">Global analysis of mouse polyomavirus infection reveals dynamic regulation of viral and host gene expression and promiscuous viral RNA editing</a>. PLOS Pathogens, 11(9), September 25.
<p>
Stoiber, M.H. et al (2015). <a href="http://genome.cshlp.org/content/early/2015/08/20/gr.182675.114.abstract">Extensive cross-regulation of posttranscriptional regulatory networks in Drosophila</a>, published onlinein Genome Research, Aug 20.
<p>
Brooks, A.N., Duff, M.O., May, G., Yang, L., Landolin, J., Wan, K., Sandler, J., Celniker, S.E., Graveley, B.R. and Brenner, S.E. (2015) <a href="http://genome.cshlp.org/content/early/2015/08/20/gr.192518.115.abstract">Regulation of alternative splicing in Drosophila by 56 RNA binding proteins</a>, published online in Genome Research, Aug 20.
<p>
Duff, M.O., Olson, S, Wei, X., Osman, A., Plocik, A., Bolisetty, M. Celniker, S. & Graveley, B.R. (2015) <a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14475.html">Genome-wide Identification of Zero Nucleotide Recursive Splicing in Drosophila</a>. Nature 521, May 21, 376-9.
<p>
Gerstein, M.B., et al (2014) <a href="http://www.nature.com/nature/journal/v512/n7515/full/nature13424.html">Comparative analysis of the transcriptome across distant species</a>. Nature 512, 445-448.
<p>
Chen, Z.X. et al (2014) <a href="http://genome.cshlp.org/cgi/pmidlookup?view=long&pmid=24985915">Comparative validation of the D. melanogaster modENCODE Transcriptome Annotation</a>. Genome Res. July;24(7):1209-23.
<p>
Brown, J.B. et al (many authors). 2014.<a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12962.html"> Diversity and dynamics of the Drosophila transcriptome</a>. Nature, published online March 16, 2014.
<p>
Eipper-Mains JE et al (2013) <a href="http://www.ncbi.nlm.nih.gov/pubmed/23094851">Effects of cocaine and withdrawal on the mouse nucleus accumbens transcriptome</a>. Genes Brain Behav.12:21-33
<p>
Smibert P, Miura P, Westholm JO, Shenker S, May G, Duff MO, Zhang D, Eads BD, Carlson J, Brown JB, Eisman R
C, Andrews J, Kaufman T, Cherbas P, Celniker SE, Graveley BR, Lai EC. (2012) <a href="http://www.cell.com/c
ell-reports/fulltext/S2211-1247(12)00021-6">Global patterns of tissue-specific alternative polyadenylation in Drosophila</a>. Cell Reports, Feb 23.
<p>
Yang L., Duff MO, Graveley BR, Carmichael GG and Chen L-L. 2011. <a href="http://genomebiology.com/2011/12/
2/R16">Genomewide characterization of long nonpolyadenylated RNAs</a>. Genome Biology, Feb 16.
<p>
Roy, S. et al (many authors). 2010. <a href="http://www.sciencemag.org/content/330/6012/1787.full">Identification of functional elements and regulatory circuits in Drosophila by large-scale data integration</a>.
Science, Dec 24.
<p>
Graveley,B.R, Brooks,A.N., Carlson,J.W., Duff,M.O., Landolin,J.M., Yang,L., et al (2010). <a href="https://www.nature.com/articles/nature09715">The developmental transcriptome of Drosophila melanogaster</a>. Nature, Dec 22.
<p>
Cherbas, L., et al (many authors). 2010. <a href="http://genome.cshlp.org/content/21/2/301.full">The transcriptional diversity of 25 Drosophila cell lines</a>. Genome Research, Dec 22.
<p>
Brooks, A.N., Yang. L., Duff, M.O., Hansen, K.D., Dudoit, S., Brenner, S.E., Graveley, B.R. 2010. <a href
="http://genome.cshlp.org/content/early/2010/10/04/gr.108662.110">Conservation of an RNA Regulatory Map between Drosophila and Mammals</a>. Genome Research, Oct 4.
<p>
McManus, C.J., Duff, M.O., Eipper-Mains, J., Graveley, B.R. 2010. <a href="http://www.pnas.org/content/107/29/12975.short">Global Analysis of Transplicing in Drosophila</a>. Proc Natl Acad Sci, July 1.
<p>
McManus, C.J., Coolon, J.D., Duff, M.O., Eipper-Mains, J., Graveley, B.R. and Wittkopp, P.J. 2010. <a href="http://www.pnas.org/content/107/29/12975.short">Regulatory Divergence in Drosophila Revealed by mRNA-Seq
</a>. Genome Research, 20(6):816-25.
<p>
Hale, C.R., Zhao, P., Olsen, S., Duff, M.O., Graveley, B.R., Wells, L., Terns, R.M., and Terns, M.P. 2009
. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19945378">RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex</a>. Cell, 139(5):945-56. Nov 25.
<p>
<br>
<p>
<br>
<p>
<br>
<img src = "mouse-maze.jpg" width="250" height="136">
<img src = "mouse-in-maze.jpg" width="250" height="136"><br>
<img src = "bamdp.jpg" width="250" height="136">
<img src = "backup.jpg" width="250" height="136">
<h3>Mostly Reinforcement Learning Theory</h3>
<ul>
<li>Y Niv, MO Duff & P Dayan (2005) - <a href="http://www.behavioralandbrainfunctions.com/content/1/1/6">Dopamine, Uncertainty and TD Learning</a> - Behavioral and Brain Functions 1:6 (4 May 2005), doi:10.1186/1744-9081-1-6.<br><p>
<li>Duff, Chudova, Wold, Smyth, & Mjolsness. <a href="http://www.sigmoid.org/publications/icsb2005.pdf">Statistical inference of biologically-plausible dynamic regulatory networks with core-leaf topology</a>, ICSB, 2005.<br><p>
<li>Duff, M.O. <a href="http://www.aaai.org/Papers/ICML/2003/ICML03-020.pdf">Design for an optimal probe<a/>. Proceedings of the 20th International Conference on Machine Learning, 2003: 131-138.<br><p>
<li>Duff, M.O. <a href="http://www.aaai.org/Papers/ICML/2003/ICML03-021.pdf">Diffusion approximation for Bayesian Markov chains</a>. Proceedings of the 20th International Conference on Machine Learning, 2003: 139-146.<br><p>
<li>Duff, M.O.
<a href="DuffThesis.pdf"> Optimal Learning: Computational procedures for Bayes-adaptive Markov decision processes</a>. Ph.D. Thesis, Dept. of Computer Science, Univ. of Massachusetts, Amherst, 2002.<br><p>
<li>Duff, M.O. <a href="duff_ai_stat_2001.pdf">
Monte-Carlo Algorithms for the Improvement of Finite-State Stochastic Controllers</a>.
Eighth International Workshop on Artificial Intelligence and Statistics, Key West FL. <br><p>
<li>Duff, M.O. <a href="A_Control_Variable_Perspective_for_the_Optimal_Com.pdf">
A Control Variable Perspective for the Optimal Combination of Truncated Corrected Returns</a>
Research Note. Department of Computer Science, University of Massachusetts, Amherst.<br><p>
<li>Duff, M.O. & Barto, A. <a href="http://papers.nips.cc/paper/1230-local-bandit-approximation-for-optimal-learning-problems.pdf">Local bandit approximation for optimal learning problems</a>. Advances in Neural Information Processing Systems 9. 1997: 1019-1025.<br><p>
<li>Duff, M.O. <a href="Duff_1995_q_learning_bandits.pdf">Q-learning for bandit problems</a>. Proceedings of the 12th International Conference on Machine Learning, 1995: 209-217.<br><p>
<li>Bradke, S. & Duff, M.O. <a href="http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=AFBA4907F489AA38EA2F9A3CAC069898?doi=10.1.1.32.9030&rep=rep1&type=pdf">Reinforcement learning methods for continuous-time Markov decision processes</a>. Advances in Neural Information Processing Systems 7. 1995: 393-400.<br><p>
<li>Duff, M.O. <a href="solving-bellmans-equation-by-solving-method-of-continuity.pdf">Solving Bellman's equation by the method of continuation</a>. Proceedings of the American Control Conference, 1994.: 2671-2682.<br><p>
<li>Barto A. & Duff, M.O. <a href="NIPS-1993-monte-carlo-matrix-inversion-and-reinforcement-learning-Paper.pdf">Monte-Carlo matrix inversion and reinforcement learning</a>. Advances in Neural Information Processing Systems, vol 6 1994: 687-694.<br><p>
<li>Duff, M.O. Backpropagation and Bach's 5th cello suite (Sarabande). Proceedings of the International Joint Conference on Neural Networks.<br><p>
<li>Szilagyi, M.O., Duff, M., & Yakowitz, S. Procedure for electron and ion lens optimization. Applied Physics Letters.<br><p>
</ul>
<p>
<br>
<!--
<a href="chrono_bio.html"><font color="#3399FF">My Erdos number is 3.</font></a>
<a href="older_papers.html"><font color="#3399FF">Other things (Machine Learning and Reinforcement Learning Theory)</font></a>
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<p>
<br>
<a href="chrono_bio.html"><font color="#3399FF">My Erdos number is 3.</font></a>
<br>
</font>
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