Browsing by Author "Liu, Y."

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Open Access
48 W continuous-wave output from a high- efficiency single emitter laser diode at 915 nm
(Institute of Electrical and Electronics Engineers, 2022-09-19) Liu, Y.; Yang, G.; Zhao, Y.; Tang, S.; Lan, Y.; Zhao, Y.; Demir, Abdullah
Improving the power and efficiency of 9xx-nm broad-area laser diodes has a great help in reducing the cost of laser systems and expanding applications. This letter presents an optimized epitaxial structure with high power and conversion efficiency. Laser diodes with 230 μm emitter width and 5 mm cavity length deliver continuous-wave output power up to 48.5 W at 48 A, 30 °C, the highest power reported for 9xx-nm single emitter lasers so far. The slope efficiency is as high as 1.23 W/A due to a low internal optical loss of 0.31 cm−1 and a high internal efficiency of 96%. The maximum power conversion efficiency reaches 72.6% at 15.3 W and 67.3% at the operating power of 30 W under a heatsink temperature of 25 °C. Life test results show no failure in 1000 hours for 55 laser diodes.
Open Access
48 W continuous-wave output power with high efficiency from a single emitter laser diode at 915 nm
(SPIE - International Society for Optical Engineering, 2023-03-14) Yang, G.; Liu, Y.; Zhao, Yongming; Tang, S.; Zhao, Yuliang; Lan, Y.; Bai, L.; Li, Y.; Wang, X.; Demir, Abdullah; Zediker, Mark S.; Zucker, Erik P.
Improving the power and efficiency of 9xx-nm broad-area laser diodes reduces the cost of laser systems and expands applications. LDs with more than 25 W output power combined with power conversion efficiency (PCE) above 65% can provide a cost-effective high-power laser module. We report a high output power and high conversion efficiency laser diode operating at 915 nm by investigating the influence of the laser internal parameters on its output. The asymmetric epitaxial structure is optimized to achieve low optical loss while considering high internal efficiency, low series resistance, and modest optical confinement factor. Experimental results show an internal optical loss of 0.31 cm-1 and internal efficiency of 96%, in agreement with our simulation results. Laser diodes with 230 μm emitter width and 5 mm cavity length have T0 and T1 characteristic temperatures of 152 and 567 K, respectively. The maximum power conversion efficiency reaches 74.2% at 5 °C and 72.6% at 25 °C, and the maximum output power is 48.5 W at 48 A (at 30 ℃), the highest reported for a 9xx-nm single emitter laser diode. At 25 oC, a high PCE of 67.5% is achieved for the operating power of 30 W at 27.5 A, and the lateral far-field angle with 95% power content is around 8°. Life test results show no failure in 1200 hours for 55 laser diodes. In addition, 55.5 W output was achieved at 55 A from a laser diode with 400 μm emitter width and 5.5 mm cavity length. A high PCE of 64.3% is obtained at 50 W with 47 A. © 2023 SPIE.
Open Access
808 nm broad-area laser diodes designed for high efficiency at high-temperature operation
(Institute of Physics Publishing Ltd., 2021-09-21) Lan, Y.; Yang, G.; Liu, Y.; Zhao, Y.; Wang, Z.; Li, T.; Demir, Abdullah
Semiconductor lasers with high power conversion efficiency (PCE) and output power are heavily investigated driven by more energy-efficient commercial applications. In this paper, an asymmetric broad area laser (A-BAL) design is studied and compared with a conventional symmetric broad area laser (S-BAL) design for 808 nm single emitter laser diodes. We present a comparative theoretical and experimental investigation by studying the thermal effects on the laser parameters. The output characteristics and efficiency loss paths for the designs were analyzed. The leakage of carriers was identified as the primary source of the PCE reduction with temperature. Suppressing this leakage by optimization of the A-BAL design, a record continuous-wave PCE of 68% at 25 °C and 60.4% at 75 °C were achieved for a single emitter laser with 10 W output power. These devices deliver high efficiency at high temperatures with reliable operation achieving 2000 h of an accelerated aging lifetime without failures.
Open Access
Chiral ceramic nanoparticles and peptide catalysis
(American Chemical Society, 2017) Jiang S.; Chekini, M.; Qu, Z.-B.; Wang Y.; Yeltik A.; Liu, Y.; Kotlyar, A.; Zhang, T.; Li, B.; Demir, Hilmi Volkan; Kotov, N. A.
The chirality of nanoparticles (NPs) and their assemblies has been investigated predominantly for noble metals and II-VI semiconductors. However, ceramic NPs represent the majority of nanoscale materials in nature. The robustness and other innate properties of ceramics offer technological opportunities in catalysis, biomedical sciences, and optics. Here we report the preparation of chiral ceramic NPs, as represented by tungsten oxide hydrate, WO3-x·H2O, dispersed in ethanol. The chirality of the metal oxide core, with an average size of ca. 1.6 nm, is imparted by proline (Pro) and aspartic acid (Asp) ligands via bio-to-nano chirality transfer. The amino acids are attached to the NP surface through C-O-W linkages formed from dissociated carboxyl groups and through amino groups weakly coordinated to the NP surface. Surprisingly, the dominant circular dichroism bands for NPs coated by Pro and Asp are different despite the similarity in the geometry of the NPs; they are positioned at 400-700 nm and 500-1100 nm for Pro- and Asp-modified NPs, respectively. The differences in the spectral positions of the main chiroptical band for the two types of NPs are associated with the molecular binding of the two amino acids to the NP surface; Asp has one additional C-O-W linkage compared to Pro, resulting in stronger distortion of the inorganic crystal lattice and greater intensity of CD bands associated with the chirality of the inorganic core. The chirality of WO3-x·H2O atomic structure is confirmed by atomistic molecular dynamics simulations. The proximity of the amino acids to the mineral surface is associated with the catalytic abilities of WO3-x·H2O NPs. We found that NPs facilitate formation of peptide bonds, leading to Asp-Asp and Asp-Pro dipeptides. The chiroptical activity, chemical reactivity, and biocompatibility of tungsten oxide create a unique combination of properties relevant to chiral optics, chemical technologies, and biomedicine.
Open Access
COMD-free continuous-wave high-power laser diodes by using the multi-section waveguide method
(SPIE - International Society for Optical Engineering, 2023-03-14) Demir, Abdullah; Ebadi, Kaveh; Liu, Y.; Sünnetçioğlu, Ali Kaan; Gündoğdu, Sinan; Şengül, Serdar; Zhao, Y.; Lan, Y.; Yang, G.; Zediker, Mark S.; Zucker, Erik P.
Catastrophic optical mirror damage (COMD) limits the output power and reliability of laser diodes (LDs). The self-heating of the laser contributes to the facet temperature, but it has not been addressed so far. This study investigates a two-section waveguide method targeting significantly reduced facet temperatures. The LD waveguide is divided into two electrically isolated sections along the cavity: laser and passive waveguide. The laser section is pumped at high current levels to achieve laser output. The passive waveguide is biased at low injection currents to obtain a transparent waveguide with negligible heat generation. This design limits the thermal impact of the laser section on the facet, and a transparent waveguide allows lossless transport of the laser to the output facet. Fabricated GaAs-based LDs have waveguide dimensions of (5-mm) x (100-µm) with passive waveguide section lengths varied from 250 to 1500 µm. The lasers were operated continuous-wave up to the maximum achievable power of around 15 W. We demonstrated that the two-section waveguide method effectively separates the heat load of the laser from the facet and results in much lower facet temperatures (Tf). For instance, at 8 A of laser current, the standard laser has Tf = 90 oC, and a two-section laser with a 1500 µm long passive waveguide section has Tf = 60 oC. While traditional LDs show COMD failures, the multi-section waveguide LDs are COMD-free. Our technique and results provide a pathway for high-reliability LDs, which would find diverse applications in semiconductor lasers. © 2023 SPIE.
Open Access
Detailed modeling of positive selection improves detection of cancer driver genes
(Nature Publishing Group, 2019-07) Zhao, S.; Liu, J.; Nanga, P.; Liu, Y.; Çiçek, A. Ercüment; Knoblauch, N.; He, C.; Stephens, M.; He, X.
Identifying driver genes from somatic mutations is a central problem in cancer biology. Existing methods, however, either lack explicit statistical models, or use models based on simplistic assumptions. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a model-based approach to driver gene identification. This method explicitly models positive selection at the single-base level, as well as highly heterogeneous background mutational processes. In particular, the selection model captures elevated mutation rates in functionally important sites using multiple external annotations, and spatial clustering of mutations. Simulations under realistic evolutionary models demonstrate the increased power of driverMAPS over current approaches. Applying driverMAPS to TCGA data of 20 tumor types, we identified 159 new potential driver genes, including the mRNA methyltransferase METTL3-METTL14. We experimentally validated METTL3 as a tumor suppressor gene in bladder cancer, providing support to the important role mRNA modification plays in tumorigenesis.
Open Access
Facet passivation process of high-power laser diodes by plasma cleaning and ZnO film
(Elsevier, 2022-09-15) Lan, Y.; Yang, G.; Zhao, Y.; Liu, Y.; Demir, Abdullah
Passivation of dangling bonds at the cleaved mirror facet and its durability are fundamental features of semiconductor lasers to obtain reliable operation with a long device lifetime. The high non-radiative recombination activity of the surface states needs to be controlled to prevent the Fermi level pinning before the deposition of mirror coating materials. Here, we report the incorporation of plasma cleaning of the facet and ZnO film as a passivation layer for the fabrication of high-power semiconductor lasers. The Argon plasma cleaning process was investigated to eliminate surface contamination without damaging the cavity surface. The ZnO passivation films were systematically studied by varying the chamber pressure and sputtering power of the radio frequency (RF) sputter coating process. We obtained homogeneous and dense ZnO films with high surface quality and optical absorption coefficient of zero. By incorporating the optimum plasma cleaning and passivation layer parameters, GaAs-based laser devices with significantly improved catastrophic optical mirror damage (COMD) power were achieved. COMD threshold was increased from 11.9 W to 20.7 W. The life test results demonstrate no failure for facet cleaned and passivated devices for more than 500 h, confirming the long-term effectiveness of the process for actual device integration.
Open Access
High-power operation and lateral divergence angle reduction of broad-area laser diodes at 976 nm
(Elsevier, 2021-04-28) Liu, Y.; Yang, G.; Wang, Z.; Li, T.; Tang, S.; Zhao, Y.; Lan, Y.; Demir, Abdullah
Broad-area diode lasers with high output power and low lateral divergence angle are highly desired for extensive scientific and industrial applications. Here, we report on the epitaxial design for higher output power and a flared waveguide design for reduced divergence, which leads to high power operation with a low lateral divergence angle. A vertically asymmetric epitaxial structure was employed and optimized for low internal optical loss and high efficiency to realize high output power operation. Using a flared waveguide design, the lateral divergence angle was efficiently reduced by decreasing the number of high-order lateral optical modes significantly. The flared waveguide design introduces a smooth modification of the ridge width along the cavity without deteriorating laser performance. Based on the optimized epitaxial and waveguide design, we scaled the waveguide width to realize high continuous-wave power of 34.5 W at 25 °C. A low lateral divergence angle of 8° and high power conversion efficiency of 60% were achieved at the operating power level of 25 W. The life test data (30 A at 45 °C for 39 units, 0 failures in 1000 h) demonstrated reliable operation illustrating the efficient design for reduced lateral divergence angle and high operating power.
Open Access
Oncogenic signaling pathways in the Cancer Genome Atlas
(Cell Press, 2018) Sanchez-Vega, F.; Mina, M.; Armenia, J.; Chatila, W. K.; Luna, A.; La, K. C.; Dimitriadoy, S.; Liu, D. L.; Kantheti, H. S.; Saghafinia, S.; Chakravarty, D.; Daian, F.; Gao, Q.; Bailey, M. H.; Liang, W. -W.; Foltz, S. M.; Shmulevich, I.; Ding, L.; Heins, Z.; Ochoa, A.; Gross, B.; Gao, J.; Zhang, H.; Kundra, R.; Kandoth, C.; Bahceci, I.; Dervishi, L.; Doğrusöz, Uğur; Zhou, W.; Shen, H.; Laird, P. W.; Way, G. P.; Greene, C. S.; Liang, H.; Xiao, Y.; Wang, C.; Iavarone, A.; Berger, A. H.; Bivona, T. G.; Lazar, A. J.; Hammer, G. D.; Giordano, T.; Kwong, L. N.; McArthur, G.; Huang, C.; Tward, A. D.; Frederick, M. J.; McCormick, F.; Meyerson, M.; Caesar-Johnson, S. J.; Demchok, J. A.; Felau, I.; Kasapi, M.; Ferguson, M. L.; Hutter, C. M.; Sofia, H. J.; Tarnuzzer, R.; Wang, Z.; Yang, L.; Zenklusen, J. C.; Zhang, J. J.; Chudamani, S.; Liu, J.; Lolla, L.; Naresh, R.; Pihl, T.; Sun, Q.; Wan, Y.; Wu, Y.; Cho, J.; DeFreitas, T.; Frazer, S.; Gehlenborg, N.; Getz, G.; Heiman, D. I.; Kim, J.; Lawrence, M. S.; Lin, P.; Meier, S.; Noble, M. S.; Saksena, G.; Voet, D.; Zhang, H.; Bernard, B.; Chambwe, N.; Dhankani, V.; Knijnenburg, T.; Kramer, R.; Leinonen, K.; Liu, Y.; Miller, M.; Reynolds, S.; Shmulevich, I.; Thorsson, V.; Zhang, W.; Akbani, R.; Broom, B. M.; Hegde, A. M.; Ju, Z.; Kanchi, R. S.; Korkut, A.; Li, J.; Liang, H.; Ling, S.; Liu W.; Lu, Y.; Mills, G. B.; Ng, K. -S.; Rao, A.; Ryan, M.; Wang, J.; Weinstein, J. N.; Zhang, J.; Abeshouse, A.; Armenia, J.; Chakravarty, D.; Chatila, W. K.; de, Bruijn, I.; Gao, J.; Gross, B. E.; Heins, Z. J.; Kundra, R.; La, K.; Ladanyi, M.; Luna, A.; Nissan, M. G.; Ochoa, A.; Phillips, S. M.; Reznik, E.; Sanchez-Vega, F.; Sander, C.; Schultz, N.; Sheridan, R.; Sumer, S. O.; Sun, Y.; Taylor, B. S.; Wang, J.; Zhang, H.; Anur, P.; Peto, M.; Spellman, P.; Benz, C.; Stuart, J. M.; Wong, C. K.; Yau, C.; Hayes, D. N.; Parker, J. S.; Wilkerson, M. D.; Ally, A.; Balasundaram, M.; Bowlby, R.; Brooks, D.; Carlsen, R.; Chuah, E.; Dhalla, N.; Holt, R.; Jones, S. J. M.; Kasaian, K.; Lee, D.; Ma, Y.; Marra, M. A.; Mayo, M.; Moore, R. A.; Mungall, A. J.; Mungall, K.; Robertson, A. G.; Sadeghi, S.; Schein, J. E.; Sipahimalani, P.; Tam, A.; Thiessen, N.; Tse, K.; Wong, T.; Berger, A. C.; Beroukhim, R.; Cherniack, A. D.; Cibulskis, C.; Gabriel, S. B.; Gao, G. F.; Ha, G.; Meyerson, M.; Schumacher, S. E.; Shih, J.; Kucherlapati, M. H.; Kucherlapati, R. S.; Baylin, S.; Cope, L.; Danilova, L.; Bootwalla, M. S.; Lai, P. H.; Maglinte, D. T.; Van, Den, Berg, D. J.; Weisenberger, D. J.; Auman, J. T.; Balu, S.; Bodenheimer, T.; Fan, C.; Hoadley, K. A.; Hoyle, A. P.; Jefferys, S. R.; Jones, C. D.; Meng, S.; Mieczkowski, P. A.; Mose, L. E.; Perou, A. H.; Perou, C. M.; Roach, J.; Shi, Y.; Simons, J. V.; Skelly, T.; Soloway, M. G.; Tan, D.; Veluvolu, U.; Fan, H.; Hinoue, T.; Laird, P. W.; Shen, H.; Zhou, W.; Bellair, M.; Chang, K.; Covington, K.; Creighton, C. J.; Dinh, H.; Doddapaneni, H.; Donehower, L. A.; Drummond, J.; Gibbs, R. A.; Glenn, R.; Hale, W.; Han, Y.; Hu, J.; Korchina, V.; Lee, S.; Lewis, L.; Li, W.; Liu, X.; Morgan, M.; Morton, D.; Muzny, D.; Santibanez, J.; Sheth, M.; Shinbrot, E.; Wang, L.; Wang, M.; Wheeler, D. A.; Xi, L.; Zhao, F.; Hess, J.; Appelbaum, E. L.; Bailey, M.; Cordes, M. G.; Ding, L.; Fronick, C. C.; Fulton, L. A.; Fulton, R. S.; Kandoth, C.; Mardis, E. R.; McLellan, M. D.; Miller, C. A.; Schmidt, H. K.; Wilson, R. K.; Crain, D.; Curley, E.; Gardner, J.; Lau, K.; Mallery, D.; Morris, S.; Paulauskis, J.; Penny, R.; Shelton, C.; Shelton, T.; Sherman, M.; Thompson, E.; Yena, P.; Bowen, J.; Gastier-Foster, J. M.; Gerken, M.; Leraas, K. M.; Lichtenberg, T. M.; Ramirez, N. C.; Wise, L.; Zmuda, E.; Corcoran, N.; Costello, T.; Hovens, C.; Carvalho, A. L.; de, Carvalho, A. C.; Fregnani, J. H.; Longatto-Filho, A.; Reis, R. M.; Scapulatempo-Neto, C.; Silveira, H. C. S.; Vidal, D. O.; Burnette, A.; Eschbacher, J.; Hermes, B.; Noss, A.; Singh, R.; Anderson, M. L.; Castro, P. D.; Ittmann, M.; Huntsman, D.; Kohl, B.; Le, X.; Thorp, R.; Andry, C.; Duffy, E. R.; Lyadov, V.; Paklina, O.; Setdikova, G.; Shabunin, A.; Tavobilov, M.; McPherson, C.; Warnick, R.; Berkowitz, R.; Cramer, D.; Feltmate, C.; Horowitz, N.; Kibel, A.; Muto, M.; Raut, C. P.; Malykh, A.; Barnholtz-Sloan, J. S.; Barrett, W.; Devine, K.; Fulop, J.; Ostrom, Q. T.; Shimmel, K.; Wolinsky, Y.; Sloan, A. E.; De, Rose, A.; Giuliante, F.; Goodman, M.; Karlan, B. Y.; Hagedorn, C. H.; Eckman, J.; Harr, J.; Myers, J.; Tucker, K.; Zach, L. A.; Deyarmin, B.; Hu, H.; Kvecher, L.; Larson, C.; Mural, R. J.; Somiari, S.; Vicha, A.; Zelinka, T.; Bennett, J.; Iacocca, M.; Rabeno, B.; Swanson, P.; Latour, M.; Lacombe, L.; Têtu, B.; Bergeron, A.; McGraw, M.; Staugaitis, S. M.; Chabot, J.; Hibshoosh, H.; Sepulveda, A.; Su, T.; Wang, T.; Potapova, O.; Voronina, O.; Desjardins, L.; Mariani, O.; Roman-Roman, S.; Sastre, X.; Stern, M. -H.; Cheng, F.; Signoretti, S.; Berchuck, A.; Bigner, D.; Lipp, E.; Marks, J.; McCall, S.; McLendon, R.; Secord, A.; Sharp, A.; Behera, M.; Brat, D. J.; Chen, A.; Delman, K.; Force, S.; Khuri, F.; Magliocca, K.; Maithel, S.; Olson, J. J.; Owonikoko, T.; Pickens, A.; Ramalingam, S.; Shin, D. M.; Sica, G.; Van, Meir, E. G.; Zhang, H.; Eijckenboom, W.; Gillis, A.; Korpershoek, E.; Looijenga, L.; Oosterhuis, W.; Stoop, H.; van, Kessel, K. E.; Zwarthoff, E. C.; Calatozzolo, C.; Cuppini, L.; Cuzzubbo, S.; DiMeco, F.; Finocchiaro, G.; Mattei, L.; Perin, A.; Pollo, B.; Chen, C.; Houck, J.; Lohavanichbutr, P.; Hartmann, A.; Stoehr, C.; Stoehr, R.; Taubert, H.; Wach, S.; Wullich, B.; Kycler, W.; Murawa, D.; Wiznerowicz, M.; Chung, K.; Edenfield, W. J.; Martin, J.; Baudin, E.; Bubley, G.; Bueno, R.; De, Rienzo, A.; Richards, W. G.; Kalkanis, S.; Mikkelsen, T.; Noushmehr, H.; Scarpace, L.; Girard, N.; Aymerich, M.; Campo, E.; Giné, E.; Guillermo, A. L.; Van, Bang, N.; Hanh, P. T.; Phu, B. D.; Tang, Y.; Colman, H.; Evason, K.; Dottino, P. R.; Martignetti, J. A.; Gabra, H.; Juhl, H.; Akeredolu, T.; Stepa, S.; Hoon, D.; Ahn, K.; Kang, K. J.; Beuschlein, F.; Breggia, A.; Birrer, M.; Bell, D.; Borad, M.; Bryce, A. H.; Castle, E.; Chandan, V.; Cheville, J.; Copland, J. A.; Farnell, M.; Flotte, T.; Giama, N.; Ho, T.; Kendrick, M.; Kocher, J. -P.; Kopp, K.; Moser, C.; Nagorney, D.; O'Brien, D.; O'Neill, B. P.; Patel, T.; Petersen, G.; Que, F.; Rivera, M.; Roberts, L.; Smallridge, R.; Smyrk, T.; Stanton, M.; Thompson, R. H.; Torbenson, M.; Yang, J. D.; Zhang, L.; Brimo, F.; Ajani, J. A.; Gonzalez, A. M. A.; Behrens, C.; Bondaruk, J.; Broaddus, R.; Czerniak, B.; Esmaeli, B.; Fujimoto, J.; Gershenwald, J.; Guo, C.; Lazar, A. J.; Logothetis, C.; Meric-Bernstam, F.; Moran, C.; Ramondetta, L.; Rice, D.; Sood, A.; Tamboli, P.; Thompson, T.; Troncoso, P.; Tsao, A.; Wistuba, I.; Carter, C.; Haydu, L.; Hersey, P.; Jakrot, V.; Kakavand, H.; Kefford, R.; Lee, K.; Long, G.; Mann, G.; Quinn, M.; Saw, R.; Scolyer, R.; Shannon, K.; Spillane, A.; Stretch, J.; Synott, M.; Thompson, J.; Wilmott, J.; Al-Ahmadie, H.; Chan, T. A.; Ghossein, R.; Gopalan, A.; Levine, D. A.; Reuter, V.; Singer, S.; Singh, B.; Tien, N. V.; Broudy, T.; Mirsaidi, C.; Nair, P.; Drwiega, P.; Miller, J.; Smith, J.; Zaren, H.; Park, J. -W.; Hung, N. P.; Kebebew, E.; Linehan, W. M.; Metwalli, A. R.; Pacak, K.; Pinto, P. A.; Schiffman, M.; Schmidt, L. S.; Vocke, C. D.; Wentzensen, N.; Worrell, R.; Yang, H.; Moncrieff, M.; Goparaju, C.; Melamed, J.; Pass, H.; Botnariuc, N.; Caraman, I.; Cernat, M.; Chemencedji, I.; Clipca, A.; Doruc, S.; Gorincioi, G.; Mura, S.; Pirtac, M.; Stancul, I.; Tcaciuc, D.; Albert, M.; Alexopoulou, I.; Arnaout, A.; Bartlett, J.; Engel, J.; Gilbert, S.; Parfitt, J.; Sekhon, H.; Thomas, G.; Rassl, D. M.; Rintoul, R. C.; Bifulco, C.; Tamakawa, R.; Urba, W.; Hayward, N.; Timmers, H.; Antenucci, A.; Facciolo, F.; Grazi, G.; Marino, M.; Merola, R.; de, Krijger, R.; Gimenez-Roqueplo, A. -P.; Piché, A.; Chevalier, S.; McKercher, G.; Birsoy, K.; Barnett, G.; Brewer, C.; Farver, C.; Naska, T.; Pennell, N. A.; Raymond, D.; Schilero, C.; Smolenski, K.; Williams, F.; Morrison, C.; Borgia, J. A.; Liptay, M. J.; Pool, M.; Seder, C. W.; Junker, K.; Omberg, L.; Dinkin, M.; Manikhas, G.; Alvaro, D.; Bragazzi, M. C.; Cardinale, V.; Carpino, G.; Gaudio, E.; Chesla, D.; Cottingham, S.; Dubina, M.; Moiseenko, F.; Dhanasekaran, R.; Becker, K. -F.; Janssen, K. -P.; Slotta-Huspenina, J.; Abdel-Rahman, M. H.; Aziz, D.; Bell, S.; Cebulla, C. M.; Davis, A.; Duell, R.; Elder, J. B.; Hilty, J.; Kumar, B.; Lang, J.; Lehman, N. L.; Mandt, R.; Nguyen, P.; Pilarski, R.; Rai, K.; Schoenfield, L.; Senecal, K.; Wakely, P.; Hansen, P.; Lechan, R.; Powers, J.; Tischler, A.; Grizzle, W. E.; Sexton, K. C.; Kastl, A.; Henderson, J.; Porten, S.; Waldmann, J.; Fassnacht, M.; Asa, S. L.; Schadendorf, D.; Couce, M.; Graefen, M.; Huland, H.; Sauter, G.; Schlomm, T.; Simon, R.; Tennstedt, P.; Olabode, O.; Nelson, M.; Bathe, O.; Carroll, P. R.; Chan, J. M.; Disaia, P.; Glenn, P.; Kelley, R. K.; Landen, C. N.; Phillips, J.; Prados, M.; Simko, J.; Smith-McCune, K.; VandenBerg, S.; Roggin, K.; Fehrenbach, A.; Kendler, A.; Sifri, S.; Steele, R.; Jimeno, A.; Carey, F.; Forgie, I.; Mannelli, M.; Carney, M.; Hernandez, B.; Campos, B.; Herold-Mende, C.; Jungk, C.; Unterberg, A.; von, Deimling, A.; Bossler, A.; Galbraith, J.; Jacobus, L.; Knudson, M.; Knutson, T.; Ma, D.; Milhem, M.; Sigmund, R.; Godwin, A. K.; Madan, R.; Rosenthal, H. G.; Adebamowo, C.; Adebamowo, S. N.; Boussioutas, A.; Beer, D.; Giordano, T.; Mes-Masson, A. -M.; Saad, F.; Bocklage, T.; Landrum, L.; Mannel, R.; Moore, K.; Moxley, K.; Postier, R.; Walker, J.; Zuna, R.; Feldman, M.; Valdivieso, F.; Dhir, R.; Luketich, J.; Pinero, E. M. M.; Quintero-Aguilo, M.; Carlotti, C. G.; Jr.; Dos, Santos, J. S.; Kemp, R.; Sankarankuty, A.; Tirapelli, D.; Catto, J.; Agnew, K.; Swisher, E.; Creaney, J.; Robinson, B.; Shelley, C. S.; Godwin, E. M.; Kendall, S.; Shipman, C.; Bradford, C.; Carey, T.; Haddad, A.; Moyer, J.; Peterson, L.; Prince, M.; Rozek, L.; Wolf, G.; Bowman, R.; Fong, K. M.; Yang, I.; Korst, R.; Rathmell, W. K.; Fantacone-Campbell, J. L.; Hooke, J. A.; Kovatich, A. J.; Shriver, C. D.; DiPersio, J.; Drake, B.; Govindan, R.; Heath, S.; Ley, T.; Van, Tine, B.; Westervelt, P.; Rubin, M. A.; Lee, J. I.; Aredes, N. D.; Mariamidze, A.; Van, Allen, E. M.; Cherniack, A. D.; Ciriello, G.; Sander, C.; Schultz, N.; The, Cancer, Genome, Atlas, Research, Network.tif
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.
Open Access
A statistical framework for mapping risk genes from de novo mutations in whole-genome-sequencing studies
(Cell Press, 2018) Liu, Y.; Liang, Y.; Çiçek, A. Ercüment; Li, Z.; Li, J.; Muhle, R. A.; Krenzer, M.; Mei, Y.; Wang Y.; Knoblauch, N.; Morrison, J.; Zhao, S.; Jiang, Y.; Geller, E.; Ionita-Laza, I.; Wu, J.; Xia, K.; Noonan, J. P.; Sun, Z. S.; He, X.
Analysis of de novo mutations (DNMs) from sequencing data of nuclear families has identified risk genes for many complex diseases, including multiple neurodevelopmental and psychiatric disorders. Most of these efforts have focused on mutations in protein-coding sequences. Evidence from genome-wide association studies (GWASs) strongly suggests that variants important to human diseases often lie in non-coding regions. Extending DNM-based approaches to non-coding sequences is challenging, however, because the functional significance of non-coding mutations is difficult to predict. We propose a statistical framework for analyzing DNMs from whole-genome sequencing (WGS) data. This method, TADA-Annotations (TADA-A), is a major advance of the TADA method we developed earlier for DNM analysis in coding regions. TADA-A is able to incorporate many functional annotations such as conservation and enhancer marks, to learn from data which annotations are informative of pathogenic mutations, and to combine both coding and non-coding mutations at the gene level to detect risk genes. It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of ∼300 autism-affected family trios across five studies and discovered several autism risk genes. The software is freely available for all research uses.