non-linear regression

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Xuhua Xia Slide 1 Non-linear regression All regression analyses are for finding the relationship between a dependent variable (y) and one or more independent variables (x), by estimating the parameters that define the relationship. Non-linear relationships whose parameters can be estimated by linear regression: e.g, y = ax b , y = ab x , y = ae bx Non-linear relationships whose parameters can be estimated by non-linear regression, e.g, Non-linear relationships that cannot be represented by a function: loess -(-) , 1 x bx y y ax e

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Non-linear regression. All regression analyses are for finding the relationship between a dependent variable (y) and one or more independent variables (x), by estimating the parameters that define the relationship. - PowerPoint PPT Presentation

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  • Non-linear regressionAll regression analyses are for finding the relationship between a dependent variable (y) and one or more independent variables (x), by estimating the parameters that define the relationship.Non-linear relationships whose parameters can be estimated by linear regression: e.g, y = axb, y = abx, y = aebxNon-linear relationships whose parameters can be estimated by non-linear regression, e.g,

    Non-linear relationships that cannot be represented by a function: loess

  • Commonly Encountered Funtions0246810121416135XYy=x1.5y=x0.5y=x105101520250246810XYy=exy=100e-xy=1000.5x

  • Growth curve of E. coliA researcher wishes to estimate the growth curve of E. coli. He put a very small number of E. coli cells into a large flask with rich growth medium, and take samples every half an hour to estimate the density (n/L).14 data points over 7 hours were obtained.What is the instantaneous rate of growth (r). What is the initial density (N0)?As the flask is very large, he assumed that the growth should be exponential, i.e., y = aebx (Which parameter correspond to r and which to N0?)

  • SAS Program/* Fictitious data */data Ecoli;Input Density @@;Time = _N_;lnD = log(Density);datalines;20.023 39.833 80.571 161.102 317.923 635.672 1284.544 2569.430 5082.654 10220.777 20673.873 40591.439 81374.642 163963.873;proc reg; var Density lnD Time; model lnD = Time; plot Density*Time/ symbol='.'; plot lnD*Time/ symbol='.';run;Run, and ask students to compute parameters a and b from regression output. What is the initial density?This statement is necessary, otherwise Density will be an unknown variable for the reg procedure and the plot statement will fail.

  • Body weight of wild elephantA researcher wishes to estimate the body weight of wild elephants. He measured the body weight of 13 captured elephants of different sizes as well as a number of predictor variables, such as leg length, trunk length, etc. Through stepwise regression, he found that the inter-leg distance (shown in figiure) is the best predictor of body weight.He learned from his former biology professor that the allometric law governing the body weight (W) and the length of a body part (L) states that W = aLb Use linear regression to find parameters a and b.

  • SAS Program/*Fitcitious data */data Elephant;Input L W @@;lnL = log(L);lnW = log(W);datalines;0.3 1.657 0.4 2.500 0.5 4.680 0.6 7.075 0.7 10.0700.8 11.988 0.9 14.836 1 18.318 1.1 23.496 1.2 27.8971.3 36.796 1.4 44.611 1.5 50.183;proc reg; var L W lnL lnW; model lnW = lnL; plot W*L/ symbol='.'; plot lnW*lnL/ symbol='.';run;Run and ask students to calculate the parameters a and b.

  • DNA and protein gel electrophoresisHow to estimate the molecular mass of a protein?A ladder: proteins with known molecular massDeriving a calibration curve relating molecular mass (M) to migration distance (D): D = F(M)Measure D and obtain MThe calibration curve is obtained by fitting a regression model

  • Protein molecular massThe equation appears to describe the relationship between D and M quite well. This relationship is better than some published relationships, e.g., D = a b ln(M)The data are my measurement of D and M for a subset of secreted proteins from the gastric pathogen Helicobacter pylori (Bumann et al., 2002).Write a SAS program to use the data to find parameters a and bBumann, D., Aksu, S., Wendland, M., Janek, K., Zimny-Arndt, U., Sabarth, N., Meyer, T.F., and Jungblut, P.R., 2002, Proteome analysis of secreted proteins of the gastric pathogen Helicobacter pylori. Infect. Immun. 70: 3396-3403.

  • Area and RadiusWhat is the functional relationship between the area and the radius?

  • Toxicity study: pesticideWhat transformation to use?

    Chart2

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    Percentage killed

    Sheet1

    These are actually my species and the order that they should be in - and the real gtRNA data.. just done manually and not including the repeatmasked numbers

    The initial files that I need to input are species specific - so this eg would be a compilation from 24 txt files

    PheAsnAspHisSerTyrCysGly

    GAAAAAGTTATTGTCATCGTGATGGCTACTGTAATAGCAACAGCCACC

    H sapiensall12321191181413015

    masked

    P troglo.all1130113109213127111

    masked

    M musculusall7141610181057141

    masked

    C familiarisall102111329892110

    masked

    F catusall822157113619128191

    masked

    B taurusall2874048622318438103531576220

    masked

    G gallusall91987166105

    masked

    T rubripesall2024241202161411218

    masked

    D rerioall19710104524150138710424142365136983611

    masked150099610750350540032002500400(eg)

    D melan.all81214569714

    masked

    C elegansall1420271919191316

    masked

    S cerevisall111116828416

    masked

    I would also like an output from each species for all tRNA comparing repeat masked and not

    Species: H sapiensSpecies: P troglodytes

    number of tRNAnumber of tRNA

    anticodongtRNAdbRM+RM-anticodongtRNAdbRM+RM-

    AlaANN302010AlaANN302010

    GNN25205GNN25205

    CNN15610056CNN15610056

    UNN12310023UNN12310023

    GlyANNGlyANN

    GNNGNN

    CNNCNN

    UNNUNN

    ProANNProANN

    GNNGNN

    CNNCNN

    UNNUNN

    ThrANNThrANN

    GNNGNN

    CNNCNN

    UNNUNN

    ValANNValANN

    GNNGNN

    CNNCNN

    UNNUNN

    SerANNSerANN

    GNNGNN

    CNNCNN

    UNNUNN

    ANNANN

    GNNGNN

    ArgANNArgANN

    GNNGNN

    CNNCNN

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    CNNCNN

    GNNGNN

    LeuANNLeuANN

    GNNGNN

    CNNCNN

    UNNUNN

    CNNCNN

    GNNGNN

    PheANNPheANN

    GNNGNN

    AsnANNAsnANN

    GNNGNN

    AspANNAspANN

    GNNGNN

    HisANNHisANN

    GNNGNN

    (etc)(etc)

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    uA(F)0.01880236141601018030280

    uA(M)-0.0188023614Disease PresentDisease absent1202036060560

    uB(F)0.09861743421Loc1Loc2Loc1Loc21803054090840

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  • Probit and probit transformationProbit has two names/definitions, both associated with standard normal distribution: the inverse cumulative distribution function (CDF)quantile functionCDF is denoted (z), which is a continuous, monotone increasing sigmoid function in the range of (0,1), e.g., (z) = p (-1.96) = 0.025 = 1 - (1.96)The probit function gives the 'inverse' computation, formally denoted -1(p), i.e., probit(p) = -1(p) probit(0.025) = -1.96 = -probit(0.975)[probit(p)] = p, and probit[(z)] = z.

    Chart3

    0.0090158468

    0.0138948343

    0.0240004059

    0.024943884

    0.064189662

    0.0778054009

    0.0915919865

    0.1020885867

    0.1171238112

    0.1623647246

    0.1690157776

    0.2293978712

    0.2735088237

    0.2744843328

    0.28144594

    0.2896518424

    0.2996213466

    0.3050358326

    0.3430269524

    0.3538935116

    0.3565072631

    0.375474145

    0.3846243207

    0.4096734332

    0.4436525048

    0.4571445565

    0.466642356

    0.4738240357

    0.4985510686

    0.5226369144

    0.551161615

    0.5611711113

    0.5767771129

    0.5999494221

    0.6030018737

    0.6050603197

    0.6182178743

    0.6199944618

    0.6292193464

    0.6605576325

    0.6714438469

    0.7058454413

    0.7157457605

    0.741110193

    0.7411630297

    0.7677296503

    0.7701377666

    0.7856495933

    0.7901377182

    0.8353484128

    0.8396291894

    0.8440291298

    0.879535989

    0.887425382

    0.9113158029

    0.9264493362

    0.9267198435

    0.9549087796

    0.9699605983

    0.971534483

    0

    1

    CDF2

    z

    CDF

    Sheet1

    These are actually my species and the order that they should be in - and the real gtRNA data.. just done manually and not including the repeatmasked numbers

    The initial files that I need to input are species specific - so this eg would be a compilation from 24 txt files

    PheAsnAspHisSerTyrCysGly

    GAAAAAGTTATTGTCATCGTGATGGCTACTGTAATAGCAACAGCCACC

    H sapiensall12321191181413015

    masked

    P troglo.all1130113109213127111

    masked

    M musculusall7141610181057141

    masked

    C familiarisall102111329892110

    masked

    F catusall822157113619128191

    masked

    B taurusall2874048622318438103531576220

    masked

    G gallusall91987166105

    masked

    T rubripesall2024241202161411218

    masked

    D rerioall19710104524150138710424142365136983611

    masked150099610750350540032002500400(eg)

    D melan.all81214569714

    masked

    C elegansall1420271919191316

    masked

    S cerevisall111116828416

    masked

    I would also like an output from each species for all tRNA comparing repeat masked and not

    Species: H sapiensSpecies: P troglodytes

    number of tRNAnumber of tRNA

    anticodongtRNAdbRM+RM-anticodongtRNAdbRM+RM-

    AlaANN302010AlaANN302010

    GNN25205GNN25205

    CNN15610056CNN15610056

    UNN12310023UNN12310023

    GlyANNGlyANN

    GNNGNN

    CNNCNN

    UNNUNN

    ProANNProANN

    GNNGNN

    CNNCNN

    UNNUNN

    ThrANNThrANN

    GNNGNN

    CNNCNN

    UNNUNN

    ValANNValANN

    GNNGNN

    CNNCNN

    UNNUNN

    SerANNSerANN

    GNNGNN

    CNNCNN

    UNNUNN

    ANNANN

    GNNGNN

    ArgANNArgANN

    GNNGNN

    CNNCNN

    UNNUNN

    CNNCNN

    GNNGNN

    LeuANNLeuANN

    GNNGNN

    CNNCNN

    UNNUNN

    CNNCNN

    GNNGNN

    PheANNPheANN

    GNNGNN

    AsnANNAsnANN

    GNNGNN

    AspANNAspANN

    GNNGNN

    HisANNHisANN

    GNNGNN

    (etc)(etc)

    Sheet2

    B

    FavorOpposeMarginal

    AF4352953.76120011573.95124371863.95483935133.757604483-8.326487131310.0692402518

    M6134954.11087386423.52636052463.91723462863.719999760211.8119933723-6.5837340108

    1048619013.942024964

    52433.95124371863.7612001157

    52433.95124371863.7612001157

    1.55769230771.8837209302-8.17187492429.8822673502

    1.55769230771.88372093029.7374388811-7.9845460966

    6.88282647586.9265704209

    DF

    u3.83741955581

    uA(F)0.01880236141601018030280

    uA(M)-0.0188023614Disease PresentDisease absent1202036060560

    uB(F)0.09861743421Loc1Loc2Loc1Loc21803054090840

    uB(O)-0.0986174342Race144123810104

    uAB(F,F)-0.19363923561Race22822201888245.660673733323.0258509299934.7322331602102.03592144991577.7410888874

    uAB(F,O)0.193639235672345828192574.499009133859.91464547112118.9974513221245.66067373333543.6445988884

    uAB(M,F)0.193639235613062934.7322331602102.03592144993397.4473353615404.98287032975656.0575891434

    uAB(M,O)-0.193639235610686

    166.504343892429.8188797975138.228274069623.0258509299483.01665351070.0000000

    93.301726284968.002933973959.914645471152.0266916421394.0056396741

    1009.4391114293601018030280

    |BlackBlondBrownRedTotal632.7794785592255.88233187282012060360560

    Female55646516200494.3245439759383.073867477880130240390840

    Male3216439100

    878010825300245.660673733323.0258509299934.7322331602102.03592144991577.7410888874

    220.4033251878266.168517335271.335172543244.361419555813.238107699259.9146454711574.4990091338245.66067373332118.99745132213543.6445988884

    110.903548889644.3614195558161.731604974819.7750211961139.0400292381Collapsed over disease350.5621307739632.77947855921315.35334160212326.79722825825656.0575891434

    388.5340063229350.5621307739505.670172529480.47189562178222104

    1059.6634733096484088427.4124

    460.51701859882845.418697156413062192Collapsed over disease

    24040280

    1711.13474239699.5121489572361.350978275768.0029339739483.016653510780480560

    185.8176485236147.5551781646394.0056396741320520840

    632.7794785592255.88233187281009.4391114293

    1315.3533416021147.55517816461577.7410888874

    12.96349350040.2746141987350.56213077392963.41732987293543.6445988884

    Collapsed over Loc1845.8627186543251.99098201925656.0575891434

    5648104

    503888427.41236221570

    10686192Collapsed over Loc

    70210280

    225.4196946812185.8176485236483.0166535107140420560

    195.6011502714138.2282740696394.0056396741210630840

    494.3245439759383.07386747781009.4391114293

    297.39466694351122.89258145071577.7410888874

    0.170348673313.0677590259691.82993916532536.90697873653543.6445988884

    Collapsed over Sp1122.89258145074060.80348621295656.0575891434

    72341060427.4123622157

    582886Collapsed over Sp

    13062192

    80130210

    307.9199605692119.8962578369494.3245439759240390630

    235.505694611793.3017262849383.0738674778320520840

    632.7794785592255.88233187281009.4391114293

    350.5621307739632.77947855921122.8925814507

    0.005057692713.23305000651315.35334160212326.79722825824060.8034862129

    1845.8627186543251.99098201925656.0575891434

    0427.4123622157

    Sheet3

    IndXX2Dosagey1y2CDF1CDF2Probit1Probit2PercentageDosagePercentage

    10.1-2.265902295527-1.6891650862-2.36496667180.04559389890.0090158468-1.6891650862-2.36496667180.90270.90

    20.2-2.105149337528-1.6319052528-2.2002428640.05134972370.0138948343-1.6319052528-2.2002428641.39281.39

    30.3-1.887640522331-1.5746454194-1.97736124060.05766915640.0240004059-1.5746454194-1.97736124062.40312.40

    40.4-1.871600533831-1.5173855859-1.96092503930.06458468050.024943884-1.5173855859-1.96092503932.49312.49

    50.5-1.441815878535-1.4601257525-1.52052403010.07212775810.064189662-1.4601257525-1.52052403016.42356.42

    60.6-1.343704630636-1.4028659191-1.41998928070.08032841270.0778054009-1.4028659191-1.41998928077.78367.78

    70.7-1.256875476937-1.3456060856-1.3310153110.0892147940.0915919865-1.3456060856-1.3310153119.16379.16

    80.8-1.197077510838-1.2883462522-1.26974024150.09881272970.1020885867-1.2883462522-1.269740241510.213810.21

    90.9-1.118760007138-1.2310864188-1.18948817280.10914527220.1171238112-1.2310864188-1.189488172811.713811.71

    101-0.918991909740-1.1738265853-0.98478549060.12023224650.1623647246-1.1738265853-0.984785490616.244016.24

    111.1-0.89291250341-1.1165667519-0.95806188180.13208980710.1690157776-1.1165667519-0.958061881816.904116.90

    121.2-0.680918492143-1.0593069185-0.74083128690.14473001260.2293978712-1.0593069185-0.740831286922.944322.94

    131.3-0.5456633344-1.002047085-0.60223511050.15816042630.2735088237-1.002047085-0.602235110527.354427.35

    141.4-0.542805095144-0.9447872516-0.59930627280.17238375080.2744843328-0.9447872516-0.599306272827.454427.45

    151.5-0.522550578744-0.8875274182-0.57855143810.18739750570.28144594-0.8875274182-0.578551438128.144428.14

    161.6-0.498983393645-0.8302675848-0.55440210660.20319375550.2896518424-0.8302675848-0.554402106628.974528.97

    171.7-0.470768118945-0.7730077513-0.52548987050.21975889660.2996213466-0.7730077513-0.525489870529.964529.96

    181.8-0.455623506445-0.7157479179-0.50997116230.23707350850.3050358326-0.7157479179-0.509971162330.504530.50

    191.9-0.352417668446-0.6584880845-0.40421597850.25511227560.3430269524-0.6584880845-0.404215978534.304634.30

    202-0.323739911546-0.601228251-0.37482983610.27384398520.3538935116-0.601228251-0.374829836135.394635.39

    212.1-0.316889801346-0.5439684176-0.36781051750.29323160310.3565072631-0.5439684176-0.367810517535.654635.65

    222.2-0.267683959647-0.4867085842-0.31738921450.31323243050.375474145-0.4867085842-0.317389214537.554737.55

    232.3-0.244231895547-0.4294487507-0.29335784760.33379834120.3846243207-0.4294487507-0.293357847638.464738.46

    242.4-0.180825394748-0.3721889173-0.2283851070.35487609850.4096734332-0.3721889173-0.22838510740.974840.97

    252.5-9.62E-0249-0.3149290839-0.14171514770.37640774930.4436525048-0.3149290839-0.141715147744.374944.37

    262.6-6.30E-0249-0.2576692504-0.10763010790.39833108980.4571445565-0.2576692504-0.107630107945.714945.71

    272.7-0.039640657249-0.200409417-0.08371288540.42058019760.466642356-0.200409417-0.083712885446.664946.66

    282.8-2.20E-0249-0.1431495836-0.06566056230.44308602310.4738240357-0.1431495836-0.065660562347.384947.38

    292.93.85E-0250-0.0858897501-0.00363194050.46577702980.4985510686-0.0858897501-0.003631940549.865049.86

    3030.097458477850-0.02862991670.05677281290.48857987590.5226369144-0.02862991670.056772812952.265052.26

    313.10.16755098510.02862991670.12859670960.51142012410.5511616150.02862991670.128596709655.125155.12

    323.20.1922824353510.08588975010.15393907060.53422297020.56117111130.08588975010.153939070656.125156.12

    333.30.2310412865520.14314958360.1936553260.55691397690.57677711290.14314958360.19365532657.685257.68

    343.40.2891663705520.2004094170.25321619060.57941980240.59994942210.2004094170.253216190659.995259.99

    353.50.2968843528520.25766925040.26112481910.60166891020.60300187370.25766925040.261124819160.305260.30

    363.60.3020980212530.31492908390.26646727330.62359225070.60506031970.31492908390.266467273360.515360.51

    373.70.3356066476530.37218891730.30080361520.64512390150.61821787430.37218891730.300803615261.825361.82

    383.80.3401568773530.42944875070.30546624280.66620165880.61999446180.42944875070.305466242862.005362.00

    393.90.3638908439530.48670858420.32978647550.68676756950.62921934640.48670858420.329786475562.925362.92

    4040.4460601456540.54396841760.41398548770.70676839690.66055763250.54396841760.413985487766.065466.06

    414.10.4752570158540.6012282510.44390356620.72615601480.67144384690.6012282510.443903566267.145467.14

    424.20.5702938518550.65848808450.54128796080.74488772440.70584544130.65848808450.541287960870.585570.58

    434.30.5985572526550.71574791790.57024951190.76292649150.71574576050.71574791790.570249511971.575571.57

    444.40.6732349345560.77300775130.64677184950.78024110340.7411101930.77300775130.646771849574.115674.11

    454.50.6733942606560.83026758480.64693511120.79680624450.74116302970.83026758480.646935111274.125674.12

    464.60.7558137059570.88752741820.73139044580.81260249430.76772965030.88752741820.731390445876.775776.77

    474.70.7635332065570.94478725160.73930063020.82761624920.77013776660.94478725160.739300630277.015777.01

    484.80.814393052581.0020470850.79141679350.84183957370.78564959331.0020470850.791416793578.565878.56

    494.90.8295022315581.05930691850.80689919340.85526998740.79013771821.05930691850.806899193479.015879.01

    5050.9940566948591.11656675190.97551840960.86791019290.83534841281.11656675190.975518409683.535983.53

    515.11.0110534606601.17382658530.99293502210.87976775350.83962918941.17382658530.992935022183.966083.96

    525.21.0288352647601.23108641881.01115606460.89085472780.84402912981.23108641881.011156064684.406084.40

    535.31.186456079611.28834625221.17267035980.90118727030.8795359891.28834625221.172670359887.956187.95

    545.41.225763972621.34560608561.21294921930.9107852060.8874253821.34560608561.212949219388.746288.74

    555.51.3584396169631.40286591911.34890216030.91967158730.91131580291.40286591911.348902160391.136391.13

    565.61.456950587641.46012575251.44984650560.92787224190.92644933621.46012575251.449846505692.646492.64

    575.71.4588461519641.51738558591.4517888940.93541531950.92671984351.51738558591.45178889492.676492.67

    585.81.6956440977661.57464541941.69443611980.94233084360.95490877961.57464541941.694436119895.496695.49

    595.91.8769444197681.63190525281.88021484360.94865027630.96996059831.63190525281.880214843697.006897.00

    6061.9691.68916508621.90383993280.95440610110.9715344831.68916508621.903839932897.156997.15

    3.050.042054236500

    1.74642491970.975893892911

    Sheet3

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    0

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    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    Percentage

    Dosage

    Percentage killed

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

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    0

    0

    CDF2

    z

    CDF

  • SAS programData Pesticide;Input Dosage Percent @@;NuProbit = probit(Percent/100);Cards;27 0.90 28 1.39 31 2.40 31 2.49 35 6.42 36 7.78 37 9.1638 10.21 38 11.71 40 16.24 41 16.90 43 22.94 44 27.35 44 27.45 44 28.14 45 28.97 45 29.96 45 30.50 46 34.30 46 35.39 46 35.65 47 37.55 47 38.46 48 40.97 49 44.37 49 45.71 49 46.66 49 47.38 50 49.86 50 52.26 51 55.12 51 56.12 52 57.68 52 59.99 52 60.30 53 60.51 53 61.8253 62.00 53 62.92 54 66.06 54 67.14 55 70.58 55 71.57 56 74.11 56 74.12 57 76.77 57 77.01 58 78.56 58 79.01 59 83.53 60 83.96 60 84.40 61 87.95 62 88.74 63 91.13 64 92.64 64 92.67 66 95.49 68 97.00 69 97.15; Proc reg; Model Percent = Dosage / R CLM alpha = 0.01 CLI; Plot Percent*Dosage / symbol = '.'; Model NuProbit = Dosage / R CLM alpha = 0.01 CLI; Plot NuProbit*Dosage / symbol = '.';run;Run and explainWhy divide Percent by 100?Graphic contrast between the original and the transformed DVCLM: CL of meanCLI: CL of individual observation

  • Commonly Encountered Funtions

  • Non-linear regressionIn rapidly replicating unicellular eukaryotes such as the yeast, highly expressed intron-containing genes requires more efficient splicing sites than lowly expressed genes.Natural selection will operate on the mutations at the slicing sites to optimize splicing efficiency.Designate splicing efficiency as SE and gene expression as GE.Certain biochemical reasoning suggests that SE and GE will follow the following relationships:

  • Guess initial valuesWhen GE=0 then SE = , so 0.4When GE increases from 2 to 8, SE increases from 0.47 to 0.75, so (0.75-0.47)/(8-2) 0.047With 0.4 and 0.047, then SE for GE = 12 should be 0.4+0.04712 = 0.96, but the actual SE is only about 0.77. This must be due to the quadratic term GE2, i.e., (0.77 - 0.96) = 122, so - 0.002

    Chart2

    0.46

    0.47

    0.57

    0.61

    0.62

    0.68

    0.69

    0.78

    0.7

    0.74

    0.77

    0.78

    0.74

    0.8

    0.8

    0.78

    SE

    GE

    SE

    Sheet1

    familyInvertebratesVertebrates

    Caenorhabditis elegansFruitflyTunicatePuffer fishZebrafishFrogMouseRatHuman

    NKX5111433222

    DLX113856766

    CDX112233323

    HOX6810454035393939

    PAX284973444

    POU352161315141316

    LIM777211412121112

    Numbers of member genes of several homeobox gene families in animal species

    Hypothesis: Gene family size is correlated with phenotypic/organismal complexity

    Sheet2

    AlaAGCGGCCGCTGC43AlaAGCCGCTGC

    29592959

    GlyACCGCCCCCTCC31GlyGCCCCCTCC

    15791579

    ProAGGGGGCGGTGG21ThrAGTCGTTGT

    10471066

    ThrAGTGGTCGTTGT22ValAACCACTAC

    106611165

    ValAACGACCACTAC32PheGAA

    1116512

    AspGTC

    19

    PheAAAGAA12GluCTCTTC

    121313

    AsnATTGTT33HisGTG

    13211

    LysCTTTTT34MetCAT

    171720

    AspATCGTC19TyrATAGTA

    19114

    GluCTCTTC26TrpCCA

    13139

    HisATGGTG11SerAGACGATGAGCT

    1111458

    GlnCTGTTG32ArgACGCCGTCGCCTTCT

    211175656

    LeuAAGCAGTAGCAATAA

    SerAGAGGACGATGAACTGCT281210377

    11458

    ArgACGGCGCCGTCGCCTTCT29

    75656

    LeuAAGGAGCAGTAGCAATAA39

    1210377

    IleAATGATTAT27

    1485

    MetCAT20

    20

    TyrATAGTA15

    114

    SupresCTATTA3

    12

    CysACAGCA30

    30

    TrpCCA9

    9

    SelCysTCA3

    3

    Sheet3

    3.365.046.728.410.0811.7613.4415.1216.818.4820.1621.8423.5225.226.8828.5630.2431.9233.6

    Fit Method kdTree

    BlendingLinear

    Number of Observations168

    Number of Fitting Points168168168168105105105656565656565414141333333

    kd Tree Bucket Size1111222333444555666

    Degree of Local Polynomials1111111111111111111

    Smoothing Parameter0.020.030.040.050.060.070.080.090.10.110.120.130.140.150.160.170.180.190.2

    Points in Local Neighborhood3568101113151618202123252628303133

    Residual Sum of Squares1.58E-29293.099468.803603.620737.152736.747868.4591057.6091196.4861335.9921451.3301452.3251539.2971584.7431613.2661629.5741629.1161629.8851637.156

    Trace[L]16872.32349.11037.10329.59929.44724.73521.14418.78616.82915.24415.17113.86412.64011.82511.06010.36310.3209.723

    GCV.0.0320.0330.0350.0380.0380.0420.0490.0540.0580.0620.0620.0650.0660.0660.0660.0660.0660.065

    AICC.3.1222.8842.8702.9282.9243.0073.1463.2323.3133.3723.3713.4113.4223.4283.4283.4183.4183.414

    AICC1.567.834496.128487.424495.105494.511507.245529.958544.085557.343567.117567.045573.492575.368576.360576.196574.486574.464573.797

    Delta1082.286110.055124.411132.582132.764138.596142.590145.565148.009149.973150.060151.668152.938153.969154.928155.724155.774156.525

    Delta2078.612108.329123.533130.021130.209136.865140.298143.795146.623148.850148.941150.739151.587152.804153.917154.664154.721155.596

    Equivalent Number of Parameters16858.93240.27530.61623.78023.65820.06716.87715.13713.66612.46012.40111.39610.2189.6189.0498.4498.4147.972

    Lookup Degrees of Freedom.86.131111.809125.295135.193135.370140.349144.919147.358149.408151.104151.187152.603154.301155.142155.946156.790156.835157.459

    Residual Standard Error.1.8872.0642.2032.3582.3562.5032.7232.8673.0043.1113.1113.1863.2193.2373.2433.2343.2353.234

    n s/ 5

    0.6721.0081.3441.682.0162.3522.6883.0243.363.6964.032

    ab

    xy58xyylnYSUMMARY OUTPUT

    000109.90777500442.2933198029

    0.10.277777777812020.01980352332.9967219598Regression Statistics

    0.20.384615384624039.93730567413.6873108664Multiple R0.9999986922

    0.30.441176470638080.22946203424.3848908044R Square0.9999973844

    0.40.47619047624160159.13598182555.0697590683Adjusted R Square0.9999971832

    0.50.55320320.60640764975.7702142264Standard Error0.0052043413

    0.60.51724137936640644.21945828796.4680394418Observations15

    0.70.5303030303712801273.2868469357.1493569046

    0.80.5405405405825602562.13554287297.8485963862ANOVA

    0.90.5487804878951205112.42618449178.539429362dfSSMSFSignificance F

    10.5555555556101024010270.7434834399.237054694Regression1134.6197795551134.61977955514970239.749071220

    1.10.5612244898112048020423.75318332139.9244538742Residual130.00035210720.0000270852

    1.20.5660377358124096040864.389560084210.6180142919Total14134.6201316622

    1.30.5701754386138192081612.379694820511.3097362414

    1.40.573770491814163840164248.2057420212.0091340123CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%

    1.50.5769230769Intercept2.30329518080.0025584336900.275547984602.29776802122.30882234052.29776802122.3088223405

    1.60.5797101449xylnYx0.69338656390.00031101892229.403451390400.69271464850.69405847930.69271464850.6940584793

    1.70.5821917808120.0232.9969

    1.80.5844155844239.8333.6847a =10.0071034002

    1.90.5864197531380.5714.3891b =0.6933865639

    20.58823529414161.1025.0820y=a*e^(bx)

    2.10.58988764045317.9235.7618exp(b) =2.000478824

    2.20.59139784956635.6726.45471.9989059382

    2.30.592783505271284.5447.1582

    2.40.594059405982569.4307.8514

    2.50.595238095295082.6548.5336SUMMARY OUTPUT

    2.60.59633027521010220.7779.2322

    2.70.59734513271120673.8739.9366Regression Statistics

    2.80.59829059831240591.43910.6113Multiple R0.9999977612

    2.90.59917355371381374.64211.3190R Square0.9999955224

    30.614163963.87312.0074Adjusted R Square0.9999951492

    3.10.6007751938Standard Error0.0063862489

    3.20.6015037594Observations14

    3.30.602189781

    3.40.6028368794ANOVA

    3.50.6034482759dfSSMSFSignificance F

    3.60.6040268456Regression1109.3003886925109.30038869252679970.583669860

    3.70.6045751634Residual120.00048941010.0000407842

    3.80.6050955414Total13109.3008781026

    3.90.6055900621

    40.6060606061CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%

    4.10.6065088757Intercept2.30281494620.0036051567638.755859529902.29495998462.31066990782.29495998462.3106699078

    4.20.6069364162x0.69313870830.00042340421637.061569908100.69221618990.69406122680.69221618990.6940612268

    4.30.6073446328

    a =10.0022987961

    b =0.6931387083

    y=a*e^(bx)

    exp(b) =1.9999830556

    xylnxlny

    0.30.803160565-1.2039728043-0.2192006287

    0.41.1339796135-0.91629073190.1257332277

    0.52.4318381914-0.69314718060.8886474288

    0.63.0625604659-0.51082562381.1192513197

    0.74.2531821711-0.35667494391.4476674489

    0.86.005437243-0.22314355131.792665266

    0.97.2742427818-0.10536051571.9843397227

    110.314799622902.3335797205

    1.112.25639649740.09531017982.5060479638

    1.214.98507490390.18232155682.7070546993

    1.317.00764518760.26236426452.8336629599

    1.421.00333015250.33647223663.0446810038

    1.525.32299803780.40546510813.2317129962

    xylnxlnySUMMARY OUTPUT

    10.31.657-1.2039728043-0.4117456216

    20.41.921-0.91629073190.4916066294Regression Statistics

    30.54.680-0.69314718060.9659051663Multiple R0.9966784784

    40.67.075-0.51082562381.150692476R Square0.9933679893

    50.710.070-0.35667494391.4543939753Adjusted R Square0.9927650793

    60.811.988-0.22314355131.8675314511Standard Error0.0914006615

    70.914.836-0.10536051572.0496882052Observations13

    8118.31802.2052853306

    91.123.4960.09531017982.4628797534ANOVA

    101.227.8970.18232155682.7124034672dfSSMSFSignificance F

    111.336.7960.26236426452.9224165743Regression113.764369002213.76436900221647.62217771160

    121.444.6110.33647223663.0246265239Residual110.09189489010.0083540809

    131.550.1830.40546510813.1356164515Total1213.8562638924

    CoefficientsStandard Errort StatP-valueLower 95%Upper 95%Lower 95.0%Upper 95.0%

    Intercept2.29535271620.027636559983.054936206702.23452505812.35618037432.23452505812.3561803743

    lnx2.12954106220.052463493240.590912501602.01406969232.24501243212.01406969232.2450124321

    a =9.9279371388

    GESEb =2.1295410622

    10.46

    20.47

    30.57

    40.61

    50.62

    60.68

    70.69

    80.78

    90.7

    100.74

    110.770.0375

    120.780.4

    130.74-1100

    130.8-1

    150.8

    160.78

    xxia:max(1, ns/5)

    xxia:int(n*s)

    Sheet3

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    SE

    GE

    SE

    MBD0764C653.unknown

  • A few more twistsThe continuity condition requires thatThe smoothness condition requires that The two conditions implies that

  • SAS program/* Fictitious data */data Intron; input SE GE @@; datalines; .46 1 .47 2 .57 3 .61 4 .62 5 .68 6 .69 7 .78 8 .70 9 .74 10 .77 11 .78 12 .74 13 .80 13 .80 15 .78 16 ; title 'Quadratic Model with Plateau';proc nlin data=Intron; parms alpha=.4 beta=.047 gamma=-.002; GE0 = -.5*beta / gamma; if (GE < GE0) then Y = alpha + beta*GE + gamma*GE*GE; else Y = alpha + beta*GE0 + gamma*GE0*GE0; model SE = Y; if _obs_ =1 and _iter_ =. then do; plateau =alpha + beta*GE0 + gamma*GE0*GE0; put / GE0= plateau= ; end; output out=b predicted=SEp; run;

    Initial guestimatesWrite out GE0 and plateau (which could be computed from the estimated , , and . However, the output of these parameters contain rounding errors.A conditional statement needed to model the two segmentscomputes predicted values for plotting and saves them to data set bRun and explain

  • Plotproc sgplot data=b noautolegend; yaxis label='Observed or Predicted'; refline 0.7775 / axis=y label="Plateau" labelpos=min; refline 12.7476 / axis=x label="GE0" labelpos=min; scatter y=SE x=GE; series y=SEp x=GE;run;

  • Fitting another function/* Fictitious data */data Intron; input SE GE @@; datalines; .46 1 .47 2 .57 3 .61 4 .62 5 .68 6 .69 7 .78 8 .70 9 .74 10 .77 11 .78 12 .74 13 .80 13 .80 15 .78 16 ; title 'Quadratic Model with Plateau';proc nlin data=Intron; parms alpha=.4 beta=.8 gamma=1; model SE = (alpha+beta*GE)/(1+gamma*GE); output out=b predicted=SEp; run;proc sgplot data=b noautolegend; yaxis label='Observed or Predicted'; scatter y=SE x=GE; series y=SEp x=GE;run;Run and explain the output

  • Plot output

  • Robust regressionLOWESS: robust local regression between Y and X, with linear fittingLOESS: robust local regression between Y and one or more Xs, with linear or quadratic fittingUsed with relations that cannot be expressed in functional formsSAS: proc loessData: Data set 1: monthly averaged atmospheric pressure differences between Easter Island and Darwin, Australia for a period of 168 months (NIST, 1998), suspected to exhibit 12-month (annual), 42-month (El Nino), and 25-month (Southern Oscillation) cycles (From Robert Cohen of SAS Institute)Data set 2: Two-channel microarray data. Background correction and two-channel loess normalization (from Wudu).

  • data ENSO;input Pressure @@;Month=_N_;datalines;12.9 11.3 10.6 11.2 10.9 7.5 7.7 11.7 12.9 14.3 10.9 13.7 17.1 14.0 15.3 8.55.7 5.5 7.6 8.6 7.3 7.6 12.7 11.0 12.7 12.9 13.0 10.9 10.4 10.2 8.0 10.913.6 10.5 9.2 12.4 12.7 13.3 10.1 7.8 4.8 3.0 2.5 6.3 9.7 11.6 8.6 12.410.5 13.3 10.4 8.1 3.7 10.7 5.1 10.4 10.9 11.7 11.4 13.7 14.1 14.0 12.5 6.39.6 11.7 5.0 10.8 12.7 10.8 11.8 12.6 15.7 12.6 14.8 7.8 7.1 11.2 8.1 6.45.2 12.0 10.2 12.7 10.2 14.7 12.2 7.1 5.7 6.7 3.9 8.5 8.3 10.8 16.7 12.612.5 12.5 9.8 7.2 4.1 10.6 10.1 10.1 11.9 13.6 16.3 17.6 15.5 16.0 15.2 11.214.3 14.5 8.5 12.0 12.7 11.3 14.5 15.1 10.4 11.5 13.4 7.5 0.6 0.3 5.5 5.04.6 8.2 9.9 9.2 12.5 10.9 9.9 8.9 7.6 9.5 8.4 10.7 13.6 13.7 13.7 16.516.8 17.1 15.4 9.5 6.1 10.1 9.3 5.3 11.2 16.6 15.6 12.0 11.5 8.6 13.8 8.78.6 8.6 8.7 12.8 13.2 14.0 13.4 14.8;ods output OutputStatistics=ENSOstats FitSummary=ENSOsummary;proc loess data=ENSO; model Pressure=Month / CLM smooth = 0.02 to 0.2 by 0.01 dfmethod=exact;run;symbol1 c=black i=join value=dot;symbol2 c=black i=join value=none;proc gplot data=ENSOstats; by SmoothingParameter; plot (DepVar Pred)*Month/overlay;run;

    Three criteria for choosing the smooth parameter:GCV: generalized cross-validation (Craven and Wahba 1979)AIC: Akaike information criterion (Akaike 1973)AICC1: bias-corrected AIC (JUrvich and Simonoff 1988)The output data ENSOstats contains variables: SoothingParameter, Month, DepVar, Pred, etc.Step 1: characterize the most obvious trend.

  • Summary output: kd Tree, linearmax(1, n*s/5)int(n*s), where n is N. Fitting Points and s is Smotthing Param.

    Sheet1

    familyInvertebratesVertebrates

    Caenorhabditis elegansFruitflyTunicatePuffer fishZebrafishFrogMouseRatHuman

    NKX5111433222

    DLX113856766

    CDX112233323

    HOX6810454035393939

    PAX284973444

    POU352161315141316

    LIM777211412121112

    Numbers of member genes of several homeobox gene families in animal species

    Hypothesis: Gene family size is correlated with phenotypic/organismal complexity

    Sheet2

    AlaAGCGGCCGCTGC43AlaAGCCGCTGC

    29592959

    GlyACCGCCCCCTCC31GlyGCCCCCTCC

    15791579

    ProAGGGGGCGGTGG21ThrAGTCGTTGT

    10471066

    ThrAGTGGTCGTTGT22ValAACCACTAC

    106611165

    ValAACGACCACTAC32PheGAA

    1116512

    AspGTC

    19

    PheAAAGAA12GluCTCTTC

    121313

    AsnATTGTT33HisGTG

    13211

    LysCTTTTT34MetCAT

    171720

    AspATCGTC19TyrATAGTA

    19114

    GluCTCTTC26TrpCCA

    13139

    HisATGGTG11SerAGACGATGAGCT

    1111458

    GlnCTGTTG32ArgACGCCGTCGCCTTCT

    211175656

    LeuAAGCAGTAGCAATAA

    SerAGAGGACGATGAACTGCT281210377

    11458

    ArgACGGCGCCGTCGCCTTCT29

    75656

    LeuAAGGAGCAGTAGCAATAA39

    1210377

    IleAATGATTAT27

    1485

    MetCAT20

    20

    TyrATAGTA15

    114

    SupresCTATTA3

    12

    CysACAGCA30

    30

    TrpCCA9

    9

    SelCysTCA3

    3

    Sheet3

    3.365.046.728.410.0811.7613.4415.1216.80000000000

    Fit Methodkd Tree

    BlendingLinear

    N168

    N. Fitting Points1681681681681051051056565

    kd Tree Bucket Size111122233

    Deg. Local Polynom.111111111

    Smoothing Param.0.020.030.040.050.060.070.080.090.1

    Neighbor Points3.05.06.08.010.011.013.015.016.0

    RSS0.0293.1468.8603.6737.2736.7868.51057.61196.5

    Trace[L]168.072.349.137.129.629.424.721.118.8

    GCV.0.00.00.00.00.00.00.00.1

    AICC.3.12.92.92.92.93.03.13.2

    AICC1.567.8496.1487.4495.1494.5507.2530.0544.1

    Delta10.082.3110.1124.4132.6132.8138.6142.6145.6

    Delta20.078.6108.3123.5130.0130.2136.9140.3143.8

    Equivalent N. Param.168.058.940.330.623.823.720.116.915.1

    Lookup DF.86.1111.8125.3135.2135.4140.3144.9147.4

    Residual SE.1.92.12.22.42.42.52.72.9

    N. Fitting Points

    kd Tree Bucket Size

    Deg. Local Polynom.

    Smoothing Param.

    Neighbor Points

    RSS

    Trace[L]

    GCV

    AICC

    AICC1

    Delta1

    Delta2

    Equivalent N. Param.

    Lookup DF

    Residual SE

    Sheet3

    1

    #REF!

    GE

    SE

    xxia:max(1, ns/5)

    xxia:int(n*s)

    xxia:max(1, ns/5)

    xxia:int(n*s)

    MBD07CC741B.unknown

    MBD0764C653.unknown

  • More on Output

  • proc loess data=ENSO; model Pressure=Month / smooth = 0.01 to 0.2 by 0.01 dfmethod=exact degree = 2;run;

  • 99% Confidence limitsods output OutputStatistics=ENSOstats FitSummary=ENSOsummary;proc loess data=ENSO; model Pressure=Month / r CLM smooth = 0.05 alpha=0.01 dfmethod=exact;run;symbol1 c=black i=none value=dot;symbol2 c=black i=join value=none;symbol3 c=red i=join value=none;symbol4 c=red i=join value=none;proc gplot data=ENSOstats; format DepVar 4.0; plot (DepVar Pred UpperCl LowerCL)*Month/ overlay hminor = 0 vminor = 0 vaxis = axis1 frame;run;

  • Pressure 0 4 8 12 16 20Month010203040506070809010011012013014015016017099% confidence limits

  • Step 2: Characterize other trends/* modify data set ENSO to filter out the 12-month cycle */data ENSO(drop=pi);set ENSO;pi = 4 * atan (1); /* or pi = 3.1415926 */cos1 = cos(2*pi*Month/12);sin1 = sin(2*pi*Month/12);proc reg data=ENSO;model Pressure = cos1 sin1;output out=ENSO1 r=FilteredPressure;run;proc print data=ENSO1; var Month Pressure FilteredPressure;run;ods output OutputStatistics=ENSO1stats;proc loess data=ENSO1;model FilteredPressure=Month/smooth = 0.12;run;proc gplot data=ENSO1stats; plot (DepVar Pred)*Month/overlay;run;r: residual, i.e., what is left after the monthly cycle has been removed.

  • Cos1 and Sin1

    Chart4

    0.86602540380.5

    0.50.8660254038

    01

    -0.50.8660254038

    -0.86602540380.5

    -10

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    Cos1

    Sin1

    Month

    Cos1, Sin1

    Sheet1

    Array RowArray ColumnX LocationY Locationch1 Intensitych1 Backgroundch2 Intensitych2 BackgroundMonthCos1Sin1ObsMonthPressureFilteredP

    1122808520469.22876166.962967231.89285354.88888910.86602540380.51112.9-0.62564

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    1160109195382.801575125.75184.15554842.925926740.50.8660254038747412.60.01604

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    1124909440528.645935113.129631247.30596965.37963178-10787811.23.61122

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    1139109410352.383942107.037041152.71084646.23148841-0848412.7-0.99455

    1141409420317134.148148140.06976344.314816850.86602540380.5858510.2-3.32564

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    1148309420374.596161145.740738167.96807946.87036988-0.50.866025403888887.1-2.43107

    1150809420362.582.138885155.54429635.65740689-0.86602540380.589895.7-2.53788

    1153109420412.77520892.898148156.98924338.86111190-1090906.7-0.88878

    11555094203523.5110.9074170520.67592691-0.8660254038-0.591913.9-3.8577

    1157809420411.926239111.240738176.58407642.18518492-0.5-0.866025403892928.5-0.19937

    1160209430424.669342131.981476151.27174444.96296393-0-193938.3-1.86148

    11625094302128.712646166.416672405.38531531.861111940.5-0.8660254038949410.8-0.95226

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    1122709695797.730591149.027771316.8266660.666668961-0969612.6-1.09455

    1124909680516.08783212.268524207.66336150.138889970.86602540380.5979712.5-1.02564

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    11297096903133.505859182.82408156453.76852990199999.8-1.32185

    11320096701405.957397109.425926303.60388251.990742100-0.50.86602540381001007.2-2.33107

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    113670967019811.75176.8981484167.26953140.166668102-1010210210.63.01122

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